期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：22
页码：13990-13995
DOI：10.1073/pnas.222433299
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Despite extensive deposition of putatively neurotoxic amyloid-{beta} (A{beta}) protein in the brain, it has not been possible to demonstrate an association of A{beta} 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 A{beta} deposition, A{beta} morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar A{beta} deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that A{beta} develops neurotoxic properties in vivo when it adopts a fibrillar {beta}-pleated sheet conformation.
