TY - JOUR
T1 - Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease
AU - Urbanc, B.
AU - Cruz, L.
AU - Le, R.
AU - Sanders, J.
AU - Hsiao Ashe, K.
AU - Duff, K.
AU - Stanley, H. E.
AU - Irizarry, M. C.
AU - Hyman, B. T.
PY - 2002/10/29
Y1 - 2002/10/29
N2 - Despite extensive deposition of putatively neurotoxic amyloid-β (Aβ) protein in the brain, it has not been possible to demonstrate an association of Aβ deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Aβ deposition, Aβ morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive Aβ fibrillar Aβ deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Aβ develops neurotoxic properties in vivo when it adopts a fibrillar β-pleated sheet conformation.
AB - Despite extensive deposition of putatively neurotoxic amyloid-β (Aβ) protein in the brain, it has not been possible to demonstrate an association of Aβ deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Aβ deposition, Aβ morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive Aβ fibrillar Aβ deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Aβ develops neurotoxic properties in vivo when it adopts a fibrillar β-pleated sheet conformation.
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U2 - 10.1073/pnas.222433299
DO - 10.1073/pnas.222433299
M3 - Article
C2 - 12374847
AN - SCOPUS:0037195163
SN - 0027-8424
VL - 99
SP - 13990
EP - 13995
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -