This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Reiss, A. B. Search for Related Content PubMed PubMed Citation Articles by Reiss, A. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Alzheimer's Disease Hazardous Substances DB CHOLESTEROL Genetics Home Reference Social Bookmarking                         What's this?

Cholesterol and apolipoprotein E in Alzheimer's disease

Vascular Biology Institute, Department of Medicine, Winthrop-University Hospital, Mineola, New York.

Alzheimer's disease (AD) is the most common cause of dementia in North America and Europe. The incidence of the disease rises dramatically with age. AD is a complex multifactorial disorder that involves numerous susceptibility genes, but the exact pathogenesis and biochemical basis of AD is not well understood. Cholesterol is receiving a great deal of attention as a potentially crucial factor in the etiology of AD. Almost all cholesterol in the brain is synthesized in the brain. Cholesterol exits the brain through the blood-brain barrier (BBB) in the form of apolipoprotein E (ApoE) or by first being converted to a more polar compound, 24(S)-hydroxycholesterol, which is elevated in individuals with AD. The key event leading to AD appears to be the formation and aggregation in the brain of amyloid ß (Aß) peptide, a proteolytically derived product of amyloid precursor protein (APP). Cholesterol has been demonstrated to modulate processing of APP to Aß. High levels of cholesterol are associated with increased risk of AD. Patients taking cholesterol-lowering statins have a lower prevalence of AD. ApoE, which transports cholesterol throughout the brain, exhibits an isoform-specific association with AD such that the E4 isoform, by unknown mechanisms, shifts the onset curve toward an earlier age.

Key Words: Alzheimer's disease • amyloid ß peptide • apolipoprotein E • cholesterol

American Journal of Alzheimer's Disease and Other Dementias®, Vol. 20, No. 2, 91-96 (2005)
DOI: 10.1177/153331750502000208


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Mast, M. A. White, I. Bjorkhem, E. F. Johnson, C. D. Stout, and I. A. Pikuleva Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain PNAS, July 15, 2008; 105(28): 9546 - 9551. [Abstract] [Full Text] [PDF]

				J C L Mamo, L Jian, A P James, L Flicker, H Esselmann, and J Wiltfang Plasma lipoprotein {beta}-amyloid in subjects with Alzheimer's disease or mild cognitive impairment Ann Clin Biochem, July 1, 2008; 45(4): 395 - 403. [Abstract] [Full Text] [PDF]

				K. Abildayeva, J. F. P. Berbee, A. Blokland, P. J. Jansen, F. J. Hoek, O. Meijer, D. Lutjohann, T. Gautier, T. Pillot, J. De Vente, et al. Human apolipoprotein C-I expression in mice impairs learning and memory functions J. Lipid Res., April 1, 2008; 49(4): 856 - 869. [Abstract] [Full Text] [PDF]

				J. S. Saczynski, L. White, R. L. Peila, B. L. Rodriguez, and L. J. Launer The Relation between Apolipoprotein A-I and Dementia: The Honolulu-Asia Aging Study Am. J. Epidemiol., May 1, 2007; 165(9): 985 - 992. [Abstract] [Full Text] [PDF]

				E. Barkus, J. Stirling, R. Hopkins, and S. Lewis The Presence of Neurological Soft Signs Along the Psychosis Proneness Continuum Schizophr Bull, July 1, 2006; 32(3): 573 - 577. [Abstract] [Full Text] [PDF]

				K. Abildayeva, P. J. Jansen, V. Hirsch-Reinshagen, V. W. Bloks, A. H. F. Bakker, F. C. S. Ramaekers, J. de Vente, A. K. Groen, C. L. Wellington,, F. Kuipers, et al. 24(S)-Hydroxycholesterol Participates in a Liver X Receptor-controlled Pathway in Astrocytes That Regulates Apolipoprotein E-mediated Cholesterol Efflux J. Biol. Chem., May 5, 2006; 281(18): 12799 - 12808. [Abstract] [Full Text] [PDF]