Charles Sanders
Faculty Member
Last active: 3/3/2020

Direct binding of cholesterol to the amyloid precursor protein: An important interaction in lipid-Alzheimer's disease relationships?

Beel AJ, Sakakura M, Barrett PJ, Sanders CR
Biochim Biophys Acta. 2010 1801 (8): 975-82

PMID: 20304095 · PMCID: PMC2886191 · DOI:10.1016/j.bbalip.2010.03.008

It is generally believed that cholesterol homoeostasis in the brain is both linked to and impacted by Alzheimer's disease (AD). For example, elevated levels of cholesterol in neuronal plasma and endosome membranes appear to be a pro-amyloidogenic factor. The recent observation that the C-terminal transmembrane domain (C99, also known as the beta-C-terminal fragment, or beta-CTF) of the amyloid precursor protein (APP) specifically binds cholesterol helps to tie together previously loose ends in the web of our understanding of Alzheimer's-cholesterol relationships. In particular, binding of cholesterol to C99 appears to favor the amyloidogenic pathway in cells by promoting localization of C99 in lipid rafts. In turn, the products of this pathway-amyloid-beta and the intracellular domain of the APP (AICD)-may down-regulate ApoE-mediated cholesterol uptake and cholesterol biosynthesis. If confirmed, this negative-feedback loop for membrane cholesterol levels has implications for understanding the function of the APP and for devising anti-amyloidogenic preventive strategies for AD.

Copyright 2010 Elsevier B.V. All rights reserved.

MeSH Terms (11)

Alzheimer Disease Amino Acid Sequence Amyloid beta-Protein Precursor Animals Cholesterol Humans Lipid Metabolism Lipids Models, Biological Molecular Sequence Data Protein Binding

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