Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions.
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.
Reiman
Eric M
EM
Banner Alzheimer's Institute and Banner Good Samaritan PET Center, Phoenix, AZ 85006, USA. eric.reiman@bannerhealth.com
Chen
Kewei
K
Caselli
Richard J
RJ
Alexander
Gene E
GE
Bandy
Daniel
D
Adamson
Jennifer L
JL
Lee
Wendy
W
Cannon
Ashley
A
Stephan
Elizabeth A
EA
Stephan
Dietrich A
DA
Papassotiropoulos
Andreas
A
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000235:genetics* / Q000502:physiology*; D002784:Cholesterol / Q000235:genetics*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012307:Risk Factors
D001057:Apolipoproteins E; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002784:Cholesterol