APOE ε4 status in healthy older African Americans is associated with deficits in pattern separation and hippocampal hyperactivation

Neha Sinha, Chelsie N. Berg, Nicholas J. Tustison, Ashlee Shaw, Diane Hill, Michael A. Yassa, Mark A. Gluck

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation—mnemonic discrimination performance and its corresponding neural computations in the hippocampus. Previous work using the mnemonic discrimination paradigm has localized increased activation in the DG/CA3 hippocampal subregions as being correlated with discrimination deficits. In a case-control high-resolution functional magnetic resonance imaging study of 30 healthy African Americans, aged 60 years and older, we observed APOE ε4–related impairments in mnemonic discrimination, coincident with dysfunctional hyperactivation in the DG/CA3, and CA1 regions, despite no evidence of structural differences in the hippocampus between carriers and noncarriers. Our results add to the growing body of evidence that deficits in pattern separation may be an early marker for AD-related neuronal dysfunction.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalNeurobiology of Aging
Volume69
DOIs
StatePublished - Sep 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Keywords

  • APOE
  • Alzheimer's disease
  • High-resolution fMRI
  • Hippocampus
  • Pattern separation

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