The role of cholesterol in the biosynthesis of beta-amyloid.

Abstract:

:Addition of the beta-hydroxy-beta-methylglutaryl-CoA (HmG-CoA) reductase inhibitor lovastatin to human HEK cells transfected with the amyloid precursor protein (APP) reduces intracellular cholesterol/protein ratios by 50%, and markedly inhibits beta-secretase cleavage of newly-synthesized APP. Exogenous water-solubilized cholesterol at 200 microg/ml concentration increases newly synthesized beta-amyloidogenic products four-fold. These intracellular changes are detectable by immunoprecipitation and immunofluorescent labelling. Analyses of the fragments captured from culture medium by an N-terminal anti-beta-amyloid antibody on ProteinChip arrays and detected using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry revealed that culture with cholesterol (200 microg/ml) increased secretion of beta-amyloid 1-40 by 1.8-fold, and increased secretion of beta-amyloid 1-42. Changes in APP processing by cholesterol may mediate the way in which the ApoE4 allele increases risk of developing Alzheimer's disease (AD) in western populations.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Frears ER,Stephens DJ,Walters CE,Davies H,Austen BM

doi

10.1097/00001756-199906030-00014

subject

Has Abstract

pub_date

1999-06-03 00:00:00

pages

1699-705

issue

8

eissn

0959-4965

issn

1473-558X

journal_volume

10

pub_type

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