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：2010
卷号：107
期号：5
页码：1942-1947
DOI：10.1073/pnas.0904532106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The formation of extracellular amyloid plaques is a common patho-biochemical event underlying several debilitating human conditions, including Alzheimer's disease (AD). Considerable evidence implies that AD damage arises primarily from small oligomeric amyloid forms of A{beta} peptide, but the precise mechanism of pathogenicity remains to be established. Using a cell culture system that reproducibly leads to the formation of Alzheimer's A{beta} amyloid plaques, we show here that the formation of a single amyloid plaque represents a template-dependent process that critically involves the presence of endocytosis- or phagocytosis-competent cells. Internalized A{beta} peptide becomes sorted to multivesicular bodies where fibrils grow out, thus penetrating the vesicular membrane. Upon plaque formation, cells undergo cell death and intracellular amyloid structures become released into the extracellular space. These data imply a mechanism where the pathogenic activity of A{beta} is attributed, at least in part, to intracellular aggregates.
关键词：Alzheimer ; aggregation ; neurodegeneration ; prion ; protein misfolding
