Correlations between apolipoprotein E ε4 gene dose and brain-imaging measurements of regional hypometabolism

Eric M. Reiman, Kewei Chen, Gene E. Alexander, Richard J. Caselli, Daniel Bandy, David Osborne, Ann M. Saunders, John Hardy

Research output: Contribution to journalArticle

295 Scopus citations

Abstract

Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgI) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) ε4 gene dose (i.e., the number of ε4 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 ε4 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 ε4 homozygotes, 46 heterozygotes, and 78 ε4 noncarriers who were individually matched for their gender, age, and educational level, we now find that ε4 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.

Original languageEnglish (US)
Pages (from-to)8299-8302
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number23
DOIs
StatePublished - Jun 7 2005

Keywords

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

ASJC Scopus subject areas

  • General

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