Optics InfoBase > Virtual Journal for Biomedical Optics > Volume 4 > Issue 5 > Page 3679
Optical visualization of Alzheimer’s pathology via multiphoton-excited intrinsic fluorescence and second harmonic generation
Alex C. Kwan, Karen Duff, Gunnar K. Gouras, and Watt W. Webb »View Author Affiliations
Alex C. Kwan,1
Karen Duff,2
Gunnar K. Gouras,3
and Watt W. Webb1,*
1School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853, USA
2Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, New York City, New York 10032, USA
3Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York City, New York 10021, USA
*Corresponding author: www2@cornell.edu
Optics Express, Vol. 17, Issue 5, pp. 3679-3689 (2009)
http://dx.doi.org/10.1364/OE.17.003679
View Full Text Article
Enhanced HTML 
Acrobat PDF (5551 KB)
Abstract
Intrinsic optical emissions, such as autofluorescence and second harmonic generation (SHG), are potentially useful for functional fluorescence imaging and biomedical disease diagnosis for neurodegenerative diseases such as Alzheimer’s disease (AD). Here, using multiphoton and SHG microscopy, we identified sources of intrinsic emissions in ex vivo, acute brain slices from AD transgenic mouse models. We observed autofluorescence and SHG at senile plaques as well as characterized their emission spectra. The utility of intrinsic emissions was demonstrated by imaging senile plaque autofluorescence in conjunction with SHG from microtubule arrays to assess the polarity of microtubules near pathological lesions. Our results suggest that tissues from AD transgenic models contain distinct intrinsic emissions, which can provide valuable information about the disease mechanisms.
© 2009 Optical Society of America
OCIS Codes
(170.0110) Medical optics and biotechnology : Imaging systems
(170.2520) Medical optics and biotechnology : Fluorescence microscopy
(170.3880) Medical optics and biotechnology : Medical and biological imaging
(170.6510) Medical optics and biotechnology : Spectroscopy, tissue diagnostics
(170.6930) Medical optics and biotechnology : Tissue
ToC Category:
Medical Optics and Biotechnology
History
Original Manuscript: October 21, 2008
Revised Manuscript: November 11, 2008
Manuscript Accepted: December 7, 2008
Published: February 24, 2009
Virtual Issues
Vol. 4, Iss. 5 Virtual Journal for Biomedical Optics
Citation
Alex C. Kwan, Karen Duff, Gunnar K. Gouras, and Watt W. Webb, "Optical visualization of Alzheimer’s pathology
via multiphoton-excited intrinsic fluorescence
and second harmonic generation," Opt. Express 17, 3679-3689 (2009)
http://www.opticsinfobase.org/vjbo/abstract.cfm?URI=oe-17-5-3679
Sort: Author | Year | Journal | Reset
References
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- E. B. Hanlon, L. T. Perelman, E. I. Vitkin, F. A. Greco, A. C. McKee, and N. W. Kowall, "Scattering differentiates Alzheimer disease in vitro," Opt. Lett. 33, 624-626 (2008). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
- J. H. Dowson, "A sensitive method for demonstration of senile plaques in the dementing brain," Histopathology 5, 305-310. (1981). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- B. Sakmann and G. Stuart, "Patch-pipette recordings from the soma, dendrites and, and axon of neurons in brain slices," in Single-Channel Recording, 2nd ed., B. Sakmann and E. Neher, eds. (Plenum, 1983), pp. 199-211.
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- J. C. Jung and M. J. Schnitzer, "Multiphoton endoscopy," Opt. Lett. 28, 902-904 (2003). [CrossRef] [PubMed]
- W. Göbel, J. N. Kerr, A Nimmerjahn, and F. Helmchen, "Miniaturized two-photon microscope based on a flexible coherent fiber and a gradient-index lens objective," Opt. Lett. 29, 2521-2523 (2004). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, "Model based and empirical spectral analysis for the diagnosis of breast cancer," Opt. Express 16, 14961-14978 (2008). [CrossRef] [PubMed]
- J. A. Palero, H. S. de Bruijn, A. van der Ploeg-van den Heuvel, H. J. C. M. Sterenborg, and H. C. Gerritsen, "In vivo nonlinear spectral imaging in mouse skin," Opt. Express 14, 4395-4402 (2006). [CrossRef] [PubMed]
Abrahamson, E. E.
Akbari, Y.
Alpár, A.
Andreadis, A.
Arendt, T.
Atwood, C. S.
Baas, P. W.
Bacskai, B. J.
Ballatore, C.
Beal, M. F.
Bi, W.
Bohl, J.
Borchelt, D. R.
Breslin, T. M.
Brückner, M. K.
Busche, M. A.
Caccamo, A.
Capetillo-Zarate, E.
Carter, C.
Chapman, P.
Chisholm, L.
Chohan, M. O.
Christie, R.
Christie, R. H.
Cole, G.
Copeland, N. G.
Corral, A.
de Bruijn, H. S.
de Calignon, A.
Deane, R.
Debnath, M. L.
DeKosky, S. T.
Denk, W.
Dickson, D. W.
Diez, M.
Dombeck, D. A.
Dowson, J. H.
Drach, L. M.
Duff, K.
Eckman, C.
Edgar, M. A.
Eichhoff, G.
Enz, A.
Erez, H.
Fisher, P. J.
Frey, P.
Games, D.
Gan, W. B.
Garaschuk, O.
Garcia-Alloza, M.
Gärtner, U.
Gerritsen, H. C.
Ghebremedhin, E.
Ginzburg, I
Göbel, W.
Goebel, H. H.
Golde, T. E.
Gonzales, V.
Gouras, G. K.
Greco, F. A.
Greengard, P.
Gremlich, H. U.
Grundke-Iqbal, I.
Grutzendler, J.
Haass, C.
Hamilton, R. L.
Han, X.
Hanlon, E. B.
Hardy, J.
Harigaya, Y.
Harter, J.
Heikal, A. A.
Helmchen, F.
Helmin, K.
Hintersteiner, M.
Hökfelt, T.
Holtzman, D. M.
Hope, C. E.
Hsiao, K.
Hutton, M.
Hyman, B. T.
Ikonomovic, M. D.
Ingelsson, M.
Iqbal, K.
Isanski, B. A.
Jaton, A. L.
Jenkins, N. A.
Jones, G.
Jung, J. C.
Kahn, K.
Kajdasz, S. T.
Kasischke, K. A.
Kayed, R.
Kerr, J. N.
Kinzy, W.
Klunk, W. E.
Kneuer, R.
Koenigsknecht-Talboo, J.
Koistinaho, J.
Kowall, N. W.
Kwan, A. C.
LaFerla, F. M.
Lee, M. K.
Lee, V. M.
Levene, M. J.
Lewis, J.
Li, B.
Li, F.
Lin, M. T.
Lin, W. L.
Lopresti, B. J.
Luo, M.
Martins, R. N.
Mathis, C. A.
Mattson, M. P.
McGowan, E.
McKee, A. C.
McLean, P. J.
Metherate, R.
Meyer-Leuhmann, M.
Meyer-Luehmann, M.
Milner, T. A.
Molloy, R. P.
Murphy, M. P.
Nam, E. E.
Nedergaard, M.
Neumann, U.
Nguyen, P. T.
Nikitin, A. Y.
Nilsen, S.
Nimmerjahn, A
Oddo, S.
Palero, J. A.
Paljug, W. R.
Perelman, L. T.
Perry, G.
Prada, C.
Price, D. L.
Price, J. C.
Qiang, L.
Ramanujam, N.
Ratovitski, T.
Rozkalne, A.
Rudin, M.
Sahara, N.
Schenk, D.
Schnitzer, M. J.
Schultz, C.
Seeger, G.
Seubert, P.
Shemesh, O. A.
Shepherd, J. D.
Sisodia, S. S.
Skipper, L.
Skoch, J.
Smith, M. A.
Spira, M. E.
Spires, T. L.
Spires-Jones, T. L.
Staufenbiel, M.
Sterenborg, H. J. C. M.
Stern, E. A.
Stoeckli, M.
Strickler, J. H.
Takahashi, R. H.
Takano, T.
Thal, D. R.
Trojanowski, J. Q.
Tsai, J.
Tsopelas, N. D.
Ueberham, U.
van der Ploeg-van den Heuvel, A.
van Lare, J.
Vishwasrao, H. D.
Vitkin, E. I.
Webb, W. W.
Wiederhold, K. H.
Williams, R. M.
Xu, H.
Yager, D.
Yamaguchi, H.
Yang, F.
Yen, S. H.
Younkin, S.
Yu, W.
Zhu, C.
Ziolko, S.
Zipfel, W. R.
Zlokovic, B.
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- J. H. Dowson, "A sensitive method for demonstration of senile plaques in the dementing brain," Histopathology 5, 305-310. (1981). [CrossRef] [PubMed]
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
Acta Neuropathol.
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
Am. J. Pathol.
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
Ann. N. Y. Acad. Sci.
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
Ann. N.Y. Acad. Sci.
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
Brain
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
Brain Res.
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
Clin. Neuropathol.
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
Dementia
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
Eur. J. Nucl. Med. Mol. Imaging
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
Histopathology
- J. H. Dowson, "A sensitive method for demonstration of senile plaques in the dementing brain," Histopathology 5, 305-310. (1981). [CrossRef] [PubMed]
J. Biol. Chem.
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
J. Neurophysiol.
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
J. Neurosci.
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
Nat. Biotechnol.
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
Nat. Med.
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
Nat. Neurosci.
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
Nat. Rev. Neurosci.
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
Nature
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
Neurobiol. Aging
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
Neuron
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
Neuroscience
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
Opt. Express
- C. Zhu, T. M. Breslin, J. Harter, and N. Ramanujam, "Model based and empirical spectral analysis for the diagnosis of breast cancer," Opt. Express 16, 14961-14978 (2008). [CrossRef] [PubMed]
- J. A. Palero, H. S. de Bruijn, A. van der Ploeg-van den Heuvel, H. J. C. M. Sterenborg, and H. C. Gerritsen, "In vivo nonlinear spectral imaging in mouse skin," Opt. Express 14, 4395-4402 (2006). [CrossRef] [PubMed]
Opt. Lett.
- E. B. Hanlon, L. T. Perelman, E. I. Vitkin, F. A. Greco, A. C. McKee, and N. W. Kowall, "Scattering differentiates Alzheimer disease in vitro," Opt. Lett. 33, 624-626 (2008). [CrossRef] [PubMed]
- J. C. Jung and M. J. Schnitzer, "Multiphoton endoscopy," Opt. Lett. 28, 902-904 (2003). [CrossRef] [PubMed]
- W. Göbel, J. N. Kerr, A Nimmerjahn, and F. Helmchen, "Miniaturized two-photon microscope based on a flexible coherent fiber and a gradient-index lens objective," Opt. Lett. 29, 2521-2523 (2004). [CrossRef] [PubMed]
Peptides
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
Proc. Natl. Acad. Sci.
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
Science
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
Traffic
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
Other
- B. Sakmann and G. Stuart, "Patch-pipette recordings from the soma, dendrites and, and axon of neurons in brain slices," in Single-Channel Recording, 2nd ed., B. Sakmann and E. Neher, eds. (Plenum, 1983), pp. 199-211.
2008, Ikonomovic, Brain
- M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, M. L. Debnath, C. E. Hope, B. A. Isanski, R. L. Hamilton, and S. T. DeKosky, "Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease," Brain 131, 1630-1645 (2008). [CrossRef] [PubMed]
- A. C. Kwan, D. A. Dombeck, and W. W. Webb, "Polarized microtubule arrays in apical dendrites and axons," Proc. Natl. Acad. Sci. 105, 11370-11375 (2008). [CrossRef] [PubMed]
- R. H. Takahashi, E. Capetillo-Zarate, M. T. Lin, T. A. Milner, and G. K. Gouras, "Co-occurrence of Alzheimer’s disease beta-amyloid and tau pathologies at synapses," Neurobiol. Aging, in press (2008).
- O. A. Shemesh, H. Erez, I Ginzburg, and M. E. Spira, "Tau-induced traffic jam reflect organelles accumulation at points of microtubule polar mismatching," Traffic 9, 458-471 (2008). [CrossRef] [PubMed]
- G. Eichhoff, M. A. Busche, and O. Garaschuk, "In vivo calcium imaging of the aging and diseased brain," Eur. J. Nucl. Med. Mol. Imaging 35, S99-S106 (2008). [CrossRef] [PubMed]
- M. Meyer-Luehmann, T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman, "Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease," Nature 451, 720-724 (2008). [CrossRef] [PubMed]
- T. Takano, X. Han, R. Deane, B. Zlokovic, and M. Nedergaard, "Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer’s disease," Ann. N.Y. Acad. Sci. 1097, 40-50 (2007). [CrossRef] [PubMed]
- J. Grutzendler, K. Helmin, J. Tsai, and W. B. Gan, "Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer’s disease," Ann. N. Y. Acad. Sci. 1097, 30-39 (2007). [CrossRef] [PubMed]
- B. Li, M. O. Chohan, I. Grundke-Iqbal, K. Iqbal, "Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau," Acta Neuropathol. 113, 501-511 (2007). [CrossRef] [PubMed]
- C. Ballatore, V. M. Lee, and J. Q. Trojanowski, "Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders," Nat. Rev. Neurosci. 8, 663-672 (2007). [CrossRef] [PubMed]
- L. Qiang, W. Yu, A. Andreadis, M. Luo, and P. W. Baas, "Tau protects microtubules in the axon from severing by katanin," J. Neurosci. 26, 3120-3129 (2006). [CrossRef] [PubMed]
- A. Alpár, U. Ueberham, M. K. Brückner, G. Seeger, T. Arendt, and U. Gärtner, "Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice," Brain Res. 1099, 189-198 (2006). [CrossRef] [PubMed]
- T. L. Spires, M. Meyer-Leuhmann, E. A. Stern, P. J. McLean, J. Skoch, P. T. Nguyen, B. J. Bacskai, B. T. Hyman, "Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy," J. Neurosci. 25, 7278-7287 (2005). [CrossRef] [PubMed]
- H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," J. Biol. Chem. 280, 25119-25126 (2005). [CrossRef] [PubMed]
- M. Hintersteiner, A. Enz, P. Frey, A. L. Jaton, W. Kinzy, R. Kneuer, U. Neumann, M. Rudin, M. Staufenbiel, M. Stoeckli, K. H. Wiederhold, and H. U. Gremlich, "In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe," Nat. Biotechnol. 23, 577-583 (2005). [CrossRef] [PubMed]
- K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305, 99-103 (2004). [CrossRef] [PubMed]
- J. Tsai, J. Grutzendler, K. Duff, and W. B. Gan, "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal brances," Nat. Neurosci. 7, 1181-1183 (2004). [CrossRef] [PubMed]
- M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, "In vivo multiphoton microscopy of deep brain tissue," J. Neurophysiol. 91, 1908-1912 (2004). [CrossRef]
- S. Oddo, A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction," Neuron 39, 409-421 (2003). [CrossRef] [PubMed]
- M. Diez, J. Koistinaho, K. Kahn, D. Games, and T. Hökfelt, "Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein - initial observations," Neuroscience 100, 259-286. (2003). [CrossRef]
- W. R. Zipfel, R. M. Williams, and W. W. Webb, "Nonlinear magic: multiphoton microscopy in the biosciences," Nat. Biotechnol. 21, 1369-1377 (2003). [CrossRef] [PubMed]
- W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, "Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation," Proc. Natl. Acad. Sci. 100, 7075-7080 (2003). [CrossRef] [PubMed]
- D. A. Dombeck, K. A. Kasischke, H. D. Vishwasrao, M. Ingelsson, B. T. Hyman, and W. W. Webb, "Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy," Proc. Natl. Acad. Sci. 100, 7081-7086 (2003). [CrossRef] [PubMed]
- D. R. Thal, E. Ghebremedhin, C. Haass, and C. Schultz, "UV light-induced autofluorescence of full-length abeta-protein deposits in the human brain," Clin. Neuropathol. 21, 35-40 (2002). [PubMed]
- R. H. Takahashi, T. A. Milner, F. Li, E. E. Nam, M. A. Edgar, H. Yamaguchi, M. F. Beal, H. Xu, P. Greengard, and G. K. Gouras, "Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology," Am. J. Pathol. 161, 1869-1879 (2002). [CrossRef] [PubMed]
- C. S. Atwood, R. N. Martins, M. A. Smith, and G. Perry, "Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins," Peptides 23, 1343-1350 (2002). [CrossRef] [PubMed]
- R. H. Christie, B. J. Bacskai, W. R. Zipfel, R. M. Williams, S. T. Kajdasz, W. W. Webb, and B. T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer’s disease observed by in vivo multiphoton microscopy," J. Neurosci. 21, 858-864 (2001). [PubMed]
- B. J. Bacskai, S. T. Kajdasz, R. H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B. T. Hyman, "Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy," Nat. Med. 7, 369-372 (2001). [CrossRef] [PubMed]
- J. Lewis, D. W. Dickson, W. L. Lin, L. Chisholm, A. Corral, G. Jones, S. H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan, "Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP," Science 293, 1487-1491 (2001). [CrossRef] [PubMed]
- D. R. Borchelt, T. Ratovitski, J. van Lare, M. K. Lee, V. Gonzales, N. A. Jenkins, N. G. Copeland, D. L. Price, and S. S. Sisodia, "Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins," Neuron 19, 939-945 (1997). [CrossRef] [PubMed]
- K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole, "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice," Science 274, 99-102 (1996). [CrossRef] [PubMed]
- L. M. Drach, J. Bohl, and H. H. Goebel, "The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer’s disease," Dementia 5, 234-239 (1994). [PubMed]
- W. Denk, J. H. Strickler, and W. W. Webb, "Two-photon laser scanning fluorescence microscopy," Science 248, 73-76 (1990). [CrossRef] [PubMed]
- J. H. Dowson, "A sensitive method for demonstration of senile plaques in the dementing brain," Histopathology 5, 305-310. (1981). [CrossRef] [PubMed]
Cited By |
 Alert me when this paper is cited |
OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.
Related Journal Articles 
- Effect of handling and fixation processes on fluorescence spectroscopy of mouse skeletal muscles under two-photon excitation (AO)
- Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherent tomography (OL)
- Absorption and scattering imaging of tissue with steady-state second-differential spectral-analysis tomography (OL)
- Three-element phased-array approach to diffuse optical imaging based on postprocessing of continuous-wave data (OL)
- Inspiratory contrast for in vivo optical imaging (OE)
Related Conference Papers
- Spatial-Frequency-Domain Imaging for Quality Assessment of Apples
- Two-Photon Microscopy with High Depth of Field Using an Axicon
- Imaging the dynamic tissue response to inhaled carbogen
- Noninvasive spectroscopic computed tomography of plants in situ using near infrared lasers
- Optical characterization of breast tumors by frequency-domain optical mammography
« Previous Article | Next Article »
OSA is a member of 
For optimal display we recommend the following web browsers:
- Firefox 11+
- Google Chrome 17+
- Internet Explorer 9+
- Safari 5+