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Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease

Papassotiropoulos, Andreas and Lambert, Jean-Charles and Wavrant-De Vrièze, Fabienne and Wollmer, M. Axel and von der Kammer, Heinz and Streffer, Johannes R. and Maddalena, Alessia and Huynh, Kim-Dung and Wolleb, Sibylle and Lutjohann, Dieter and Schneider, Brigitte and Thal, Dietmar R. and Grimaldi, Luigi M. E. and Tsolaki, Magdalini and Kapaki, Elisabeth and Ravid, Rivka and Konietzko, Uwe and Hegi, Thomas and Pasch, Thomas and Jung, Hans and Braak, Heiko and Amouyel, Philippe and Rogaev, Evgeny I. and Hardy, John and Hock, Christoph and Nitsch, Roger M.. (2005) Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease. Neuro-degenerative Diseases, 2 (5). pp. 233-241.

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Official URL: http://edoc.unibas.ch/dok/A5257165

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Karger
ISSN:1660-2854
e-ISSN:1660-2862
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:11 Oct 2017 13:15
Deposited On:22 Mar 2012 13:17

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