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Papassotiropoulos, A; Lambert, J C; Wavrant-De Vrièze, F; Wollmer, M A; von der Kammer, H; Streffer, J R; Maddalena, A; Huynh, K D; Wolleb, S; Lütjohann, D; Schneider, B; Thal, D R; Grimaldi, L M E; Tsolaki, M; Kapaki, E; Ravid, R; Konietzko, U; Hegi, T; Pasch, T; Jung, H; Braak, H; Amouyel, P; Rogaev, E I; Hardy, J; Hock, C; Nitsch, R M (2005). Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease. Neuro-degenerative Diseases, 2(5):233-241.

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Abstract

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.

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19 citations in Web of Science®
22 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
DDC:610 Medicine & health
Language:English
Date:2005
Deposited On:09 Sep 2011 14:20
Last Modified:28 Oct 2014 16:01
Publisher:Karger
ISSN:1660-2854
Publisher DOI:10.1159/000090362
PubMed ID:16909003

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