Alzheimer's disease β-amyloid peptides are released in association with exosomes

Lawrence Rajendran, Masanori Honsho, Tobias R. Zahn, Patrick Keller, Kathrin D. Geiger, Paul Verkade, Kai Simons

研究成果: Contribution to journalArticle査読

834 被引用数 (Scopus)

抄録

Although the exact etiology of Alzheimer's disease (AD) is a topic of debate, the consensus is that the accumulation of β-amyloid (Aβ) peptides in the senile plaques is one of the hallmarks of the progression of the disease. The Aβ peptide is formed by the amyloidogenic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. The endocytic system has been implicated, in the cleavages leading to the formation of Aβ. However, the identity of the intracellular compartment where the amyloidogenic secretases cleave and the mechanism by which the intracellularly generated Aβ is released into the extracellular milieu are not clear. Here, we show that β-cleavage occurs in early endosomes followed by routing of Aβ to multivesicular bodies (MVBs) in HeLa and N2a cells. Subsequently, a minute fraction of Aβ peptides can be secreted from the cells in association with exosomes, intraluminal vesicles of MVBs that are released into the extracellular space as a result of fusion of MVBs with the plasma membrane. Exosomal proteins were found to accumulate in the plaques of AD patient brains, suggesting a role in the pathogenesis of AD.

本文言語英語
ページ(範囲)11172-11177
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
103
30
DOI
出版ステータス出版済み - 7 25 2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

フィンガープリント

「Alzheimer's disease β-amyloid peptides are released in association with exosomes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル