Knockdown of ACAT-1 reduces amyloidogenic processing of APP.

FEBS letters (2007-04-07)
Henri J Huttunen, Christopher Greco, Dora M Kovacs
ABSTRACT

Previous studies have shown that acyl-coenzyme A:cholesterol acyl transferase (ACAT), an enzyme that controls cellular equilibrium between free cholesterol and cholesteryl esters, modulates proteolytic processing of APP in cell-based and animal models of Alzheimer's disease. Here we report that ACAT-1 RNAi reduced cellular ACAT-1 protein by approximately 50% and cholesteryl ester levels by 22% while causing a slight increase in the free cholesterol content of ER membranes. This correlated with reduced proteolytic processing of APP and 40% decrease in Abeta secretion. These data show that even a modest decrease in ACAT activity can have robust suppressive effects on Abeta generation.

MATERIALS
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Product Description

Sigma-Aldrich
Anti-Amyloid Precursor Protein, C-Terminal antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution