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Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions

Reiman, Eric M. and Chen, Kewei and Caselli, Richard J. and Alexander, Gene E. and Bandy, Daniel and Adamson, Jennifer L. and Lee, Wendy and Cannon, Ashley and Stephan, Elizabeth A. and Stephan, Dietrich A. and Papassotiropoulos, Andreas. (2008) Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions. NeuroImage, Vol. 40, H. 3. pp. 1214-1221.

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Official URL: http://edoc.unibas.ch/dok/A5257147

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Abstract

We recently implicated a cluster of nine single nucleotide polymorphisms from seven cholesterol-related genes in the risk of Alzheimer's disease (AD) in a European cohort, and we proposed calculating an aggregate cholesterol-related genetic score (CREGS) to characterize a person's risk. In a separate study, we found that apolipoprotein E (APOE) epsilon4 gene dose, an established AD risk factor, was correlated with fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of hypometabolism in AD-affected brain regions in a cognitively normal American cohort, and we proposed using PET as a presymptomatic endophenotype to help assess putative modifiers of AD risk. Thus, the objective in the present study is to determine whether CREGS is related to PET measurements of hypometabolism in AD-affected brain regions. DNA and PET data from 141 cognitively normal late middle-aged APOE epsilon4 homozygotes, heterozygotes and noncarriers were analyzed to evaluate the relationship between CREGS and regional PET measurements. Cholesterol-related genetic risk scores were associated with hypometabolism in AD-affected brain regions, even when controlling for the effects of APOE epsilon4 gene dose. The results support the role of cholesterol-related genes in the predisposition to AD and support the value of neuroimaging in the presymptomatic assessment of putative modifiers of AD risk.
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:Elsevier
ISSN:1095-9572
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:20
Deposited On:22 Mar 2012 13:17

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