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Alzheimer's disease: the cholesterol connection.
Nat Neurosci 2003; 6(4):345-51NN

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.

Authors+Show Affiliations

Neurobiology of Disease Laboratory, CAGN, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

12658281

Citation

Puglielli, Luigi, et al. "Alzheimer's Disease: the Cholesterol Connection." Nature Neuroscience, vol. 6, no. 4, 2003, pp. 345-51.
Puglielli L, Tanzi RE, Kovacs DM. Alzheimer's disease: the cholesterol connection. Nat Neurosci. 2003;6(4):345-51.
Puglielli, L., Tanzi, R. E., & Kovacs, D. M. (2003). Alzheimer's disease: the cholesterol connection. Nature Neuroscience, 6(4), pp. 345-51.
Puglielli L, Tanzi RE, Kovacs DM. Alzheimer's Disease: the Cholesterol Connection. Nat Neurosci. 2003;6(4):345-51. PubMed PMID: 12658281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alzheimer's disease: the cholesterol connection. AU - Puglielli,Luigi, AU - Tanzi,Rudolph E, AU - Kovacs,Dora M, PY - 2003/01/29/received PY - 2003/02/27/accepted PY - 2003/3/27/pubmed PY - 2003/6/11/medline PY - 2003/3/27/entrez SP - 345 EP - 51 JF - Nature neuroscience JO - Nat. Neurosci. VL - 6 IS - 4 N2 - 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. SN - 1097-6256 UR - https://www.unboundmedicine.com/medline/citation/12658281/Alzheimer's_disease:_the_cholesterol_connection_ L2 - http://dx.doi.org/10.1038/nn0403-345 DB - PRIME DP - Unbound Medicine ER -