The apolipoprotein E epsilon 4 allele is associated with ventricular expansion rate and surface morphology in dementia and normal aging

Florence F. Roussotte, Boris A. Gutman, Sarah K. Madsen, John B. Colby, Katherine L. Narr, Paul M. Thompson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The apolipoprotein E epsilon 4 allele (ApoE-ε4) is the strongest known genetic risk factor for late onset Alzheimer's disease. Expansion of the lateral ventricles occurs with normal aging, but dementia accelerates this process. Brain structure and function depend on ApoE genotype not just for Alzheimer's disease patients but also in healthy elderly individuals, and even in asymptomatic young individuals. Therefore, we hypothesized that the ApoE-ε4 allele is associated with altered patterns of longitudinal ventricular expansion, in dementia and normal aging. We tested this hypothesis in a large sample of elderly participants, using a linear discriminant analysis-based approach. Carrying more ApoE-ε4 alleles was associated with faster ventricular expansion bilaterally and with regional patterns of lateral ventricle morphology at 1- and 2-year follow up, after controlling for sex, age, and dementia status. ApoE genotyping is considered critical in clinical trials of Alzheimer's disease. These findings, combined with earlier investigations showing that ApoE is also directly implicated in other conditions, suggest that the selective enrollment of ApoE-ε4 carriers may empower clinical trials of other neurological disorders.

Original languageEnglish
Pages (from-to)1309-1317
Number of pages9
JournalNeurobiology of Aging
Volume35
Issue number6
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • ApoE
  • Dementia
  • Neuroimaging genetics
  • Structural MRI
  • Ventricular expansion

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