Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Reiman, EM; Chen, K; Alexander, GE; Caselli, RJ; Bandy, D; Osborne, D; Saunders, AM; Hardy, J

Published Date

  • June 2, 2005

Published In

Volume / Issue

  • 102 / 23

Start / End Page

  • 8299 - 8302

PubMed ID

  • 15932949

Pubmed Central ID

  • 15932949

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0500579102

Language

  • eng