Journal article

Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes

Robyn A Sharples, Laura J Vella, Rebecca M Nisbet, Ryan Naylor, Keyla Perez, Kevin J Barnham, Colin L Masters, Andrew F Hill

FASEB JOURNAL | FEDERATION AMER SOC EXP BIOL | Published : 2008

Abstract

Alzheimer's disease (AD) is the most common form of dementia and is associated with the deposition of the 39- to 43-amino acid beta-amyloid peptide (Abeta) in the brain. C-terminal fragments (CTFs) of amyloid precursor protein (APP) can accumulate in endosomally derived multivesicular bodies (MVBs). These intracellular structures contain intraluminal vesicles that are released from the cell as exosomes when the MVB fuses with the plasma membrane. Here we have investigated the role of exosomes in the processing of APP and show that these vesicles contain APP-CTFs, as well as Abeta. In addition, inhibition of gamma-secretase results in a significant increase in the amount of alpha- and beta-se..

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