Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism.
Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE epsilon4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia. In a PET study of 160 cognitively normal subjects 47-68 years of age, including 36 epsilon4 homozygotes, 46 heterozygotes, and 78 epsilon4 noncarriers who were individually matched for their gender, age, and educational level, we now find that epsilon4 gene dose is correlated with lower CMRgl in each of these brain regions. This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.
Reiman
Eric M
EM
Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA. eric.reiman@bannerhealth.com
Chen
Kewei
K
Alexander
Gene E
GE
Caselli
Richard J
RJ
Bandy
Daniel
D
Osborne
David
D
Saunders
Ann M
AM
Hardy
John
J
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D049268:Positron-Emission Tomography
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005947:Glucose