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

Eric M. Reiman, Kewei Chen, Richard J. Caselli, Gene E. Alexander, Daniel Bandy, Jennifer L. Adamson, Wendy Lee, Ashley Cannon, Elizabeth A. Stephan, Dietrich A. Stephan, Andreas Papassotiropoulos
2008 NeuroImage  
We recently implicated a cluster of nine single nucleotide polymorphisms from seven cholesterolrelated 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) ε4 gene dose, an established AD risk factor, was correlated with fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of
more » ... m 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 ε4 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 ε4 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.
doi:10.1016/j.neuroimage.2007.12.066 pmid:18280754 pmcid:PMC2441925 fatcat:odwj5jtkxvhhffjv3wtzemkala