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Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7. PubMed.
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Lund University
Rajendran and colleagues provide further insights into the biology of Alzheimer disease (AD). They present more evidence for endosomes as important sites of Aβ generation using elegant cell biology experiments. By crosslinking experiments, they show that there was increased colocalization of APP with BACE in early endosomes. Aβ secretion was dramatically reduced by inhibiting endocytosis or reducing recycling. They provide further confirmation for Aβ localization to multivesicular bodies (MVBs) by immunoelectron microscopy and present exciting new data on Aβ in secreted exosomes. It has been described that in some cells MVBs can fuse with the plasma membrane and secrete their inner (luminal) vesicles (exosomes). Interestingly, the authors localize the exosome component Alix to plaques in AD brain, and note that flottilin-1, known to be contained in exosomes, was previously shown to associate with plaques. Yet, they point out that, at least in APP transfected neuroblastoma cells, exosome-associated Aβ appears to account for only about 1 percent of Aβ secreted. They hypothesize that in the slowly progressive disease process, secreted exosome-associated Aβ may be important in the progression of the disease. Despite evidence in support of intraneuronal MVB Aβ involvement in plaque formation, the authors did not consider the alternative—that plaque-associated Alix and flotillin-1, which localize to exosomes and MVB inner vesicles, could originate from MVBs without being secreted.
View all comments by Gunnar GourasJohns Hopkins Univ School of Medicine
I strongly recommend this article. But what percent of amyloid-β is bound to exosomes in AD is still shrouded in mystery. Much more experimental data are required to understand this better.
View all comments by Bharathi Shrikanth GadadMake a Comment
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