TY - JOUR
T1 - Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions
AU - Reiman, Eric M.
AU - Chen, Kewei
AU - Caselli, Richard J.
AU - Alexander, Gene E.
AU - Bandy, Daniel
AU - Adamson, Jennifer L.
AU - Lee, Wendy
AU - Cannon, Ashley
AU - Stephan, Elizabeth A.
AU - Stephan, Dietrich A.
AU - Papassotiropoulos, Andreas
N1 - Funding Information:
This study was presented in July 2006 at the 10 th International Conference on Alzheimer's Disease and Related Disorders, Madrid. It was supported by the National Institute of Mental Health (RO1 MH57899 to EMR), the National Institute on Aging (EMR, P30 AG19610), the Arizona Alzheimer's Consortium (Arizona Department of Health Services to EMR), the Banner Alzheimer Foundation (to EMR), the Mayo Clinic Foundation (to RJC), the Swiss National Science Foundation (PP00B-68859 to AP), the Helmut-Horten Stiftung (to AP), the EMDO Stiftung (to AP) and the Novartis Foundation for Biomedical Research (to AP). We thank Christine Burns, Sandra Yee-Benedetto, Carolyn Barbieri, Alisa Domb, Sandra Goodwin, Debbie Intorcia, Barbara Knight, Leslie Mullen, Anita Prouty, Oded Smilovici, Cole Reschke, Desiree Van Egmond, Katy Venisnik, Dr. Jessica Langbaum and Dr. Michael Hutton for their technical assistance.
PY - 2008/4/15
Y1 - 2008/4/15
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cholesterol
KW - Endophenotype
KW - Genetics
KW - Positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=40849111266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40849111266&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2007.12.066
DO - 10.1016/j.neuroimage.2007.12.066
M3 - Article
C2 - 18280754
AN - SCOPUS:40849111266
SN - 1053-8119
VL - 40
SP - 1214
EP - 1221
JO - NeuroImage
JF - NeuroImage
IS - 3
ER -