Journal of Alzheimer's Disease
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Home > Localization and Processing of the Amyloid-β Protein Precursor in Mitochondria-Associated Membranes.

TitleLocalization and Processing of the Amyloid-β Protein Precursor in Mitochondria-Associated Membranes.
Publication TypeJournal Article
Year of Publication2017
AuthorsDel Prete, D, Suski, JM, Oulès, B, Debayle, D, Gay, ASophie, Lacas-Gervais, S, Bussiere, R, Bauer, C, Pinton, P, Paterlini-Bréchot, P, Wieckowski, MR, Checler, F, Chami, M
JournalJ Alzheimers Dis
Volume55
Issue4
Pagination1549-1570
Date Published2017
ISSN1875-8908
Abstract

Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD. Furthermore, we evidenced that both β- and γ-secretases are present and harbor AβPP processing activities in MAMs. Interestingly, cells overexpressing APPswe show increased ER-mitochondria contact sites. We also document increased neutral lipid accumulation linked to Aβ production and reversed by inhibiting β- or γ-secretases. Using a proteomic approach, we show that AβPP and its catabolites interact with key proteins of MAMs controlling mitochondria and ER functions. These data highlight the role of AβPP processing and proteomic interactome in MAMs deregulation taking place in AD.

DOI10.3233/JAD-160953
Alternate JournalJ. Alzheimers Dis.
PubMed ID27911326
PubMed Central IDPMC5181669
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Source URL: https://www.j-alz.com/content/localization-and-processing-%C2%A0%C2%A0amyloid-%CE%B2-protein-precursor-%C2%A0mitochondria-associated-membranes