Effect of APOE ϵ4 Genotype on Metabolic Biomarkers in Aging and Alzheimer's Disease

Jill K. Morris, Roxanne Adeline Z. Uy, Eric D. Vidoni, Heather M. Wilkins, Ashley E. Archer, John P. Thyfault, John M. Miles, Jeffrey M. Burns

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Alzheimer's disease (AD) may have heterogeneous pathophysiological underpinnings, with risk factors including apolipoprotein rmvarep4 (APOE4) genotype and insulin resistance. We hypothesized that distinct phenotypes exist within AD. We examined APOE4 and metabolic biomarkers in 338 subjects (n = 213 nondemented (ND), n = 125 AD). We further characterized steady state free fatty acid (FFA) levels in a subset of 45 participants who had also participated in a hyperinsulinemic-euglycemic clamp. Insulin resistance (HOMA-IR) was elevated in AD versus ND (p = 0.04) and in APOE4 noncarriers versus carriers (p < 0.01). This was driven by increased fasting insulin in AD versus ND (p < 0.01) and in APOE4 non-carriers versus carriers (p = 0.01). Fasting glucose was not different. In subjects who underwent a clamp, there was a group x genotype interaction on FFA levels during hyperinsulinemia (p = 0.03). APOE4 non-carriers with AD had higher FFA levels, while APOE4 carriers with AD exhibited lower FFA levels. Metabolic dysfunction is overrepresented in individuals with AD dementia who do not carry the APOE4 allele. This suggests that important subsets of AD phenotypes may exist that diverge metabolically.

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2017


  • Alzheimer's disease
  • apolipoprotein E
  • hyperinsulinemia
  • insulin
  • insulin resistance

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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