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Alzheimer’s disease: the cholesterol connection

Puglielli, Luigi, Tanzi, Rudolph E., Kovacs, Dora M.·2003·Nature Neuroscience
DOI 10.1038/nn0403-345
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Abstract

A hallmark of all forms of Alzheimer's disease (AD) is an abnormal accumulation of the beta-amyloid protein (Abeta) in specific brain regions. Both the generation and clearance of Abeta are regulated by cholesterol. Elevated cholesterol levels increase Abeta in cellular and most animals models of AD, and drugs that inhibit cholesterol synthesis lower Abeta in these models. Recent studies show that not only the total amount, but also the distribution of cholesterol within neurons, impacts Abeta biogenesis. The identification of a variant of the apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD. Clinical trials have recently been initiated to test whether lowering plasma and/or neuronal cholesterol levels is a viable strategy for treating and preventing AD. In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection.

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Metadata

Authors
Puglielli, L., Tanzi, R. E., & Kovacs, D. M.
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2003-04
Volume
6
Issue
4
Pages
345-351
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/nn0403-345
Cited by
677
References
5
Language
en
Licence
www.springer.com/tdm (tdm)

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