Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer's disease.

Abstract:

:There is much evidence suggesting that there is a strong relationship between the deterioration of brain lipid homeostasis, vascular changes and the pathogenesis of Alzheimer's disease (AD). These associations include: (1). recognition that a key cholesterol transporter, apolipoprotein E type 4, acts a major genetic risk factor for both familial and sporadic AD; (2). epidemiological studies linking cardiovascular risk factors, such as hypertension and high plasma cholesterol, to dementia; (3). the discovery that small strokes can precipitate clinical dementia in cognitively normal elderly subjects; (4). the modulation of degradation of the amyloid precursor protein by cholesterol administration in cell culture and in animal models of beta-amyloid overproduction; and (5). the beneficial effect of cholesterol-lowering drugs, such as Probucol and statins, in combating common AD. The recent finding that there is a genetic association between the HMGR gene locus and sporadic AD further suggests that brain cholesterol metabolism is central to AD pathophysiology, and a potential therapeutic target for disease stabilization and primary disease prevention.

journal_name

Trends Mol Med

authors

Poirier J

doi

10.1016/s1471-4914(03)00007-8

keywords:

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

94-101

issue

3

eissn

1471-4914

issn

1471-499X

pii

S1471491403000078

journal_volume

9

pub_type

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