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

Research output: Contribution to journalArticle

24 Scopus citations

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) e{open}4 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 e{open}4 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 e{open}4 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.

Original languageEnglish (US)
Pages (from-to)1214-1221
Number of pages8
JournalNeuroImage
Volume40
Issue number3
DOIs
StatePublished - Apr 15 2008

Keywords

  • Alzheimer's disease
  • Cholesterol
  • Endophenotype
  • Genetics
  • Positron emission tomography

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

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    Reiman, E. M., Chen, K., Caselli, R. J., Alexander, G. E., Bandy, D., Adamson, J. L., Lee, W., Cannon, A., Stephan, E. A., Stephan, D. A., & Papassotiropoulos, A. (2008). Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions. NeuroImage, 40(3), 1214-1221. https://doi.org/10.1016/j.neuroimage.2007.12.066