Few serum proteins mediate APOE's association with dementia

Donald R. Royall, Safa Al-Rubaye, Ram Bishnoi, Raymond F. Palmer

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of APOE's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). APOE was associated only with C-Reactive Protein (CRP), Adiponectin (APN) and Amphiregulin (AREG), although the latter two's associations did not survive Bonferroni correction for multiple comparisons. All three proteins were associated with δ and had weak potential mediation effects on APOE's association with that construct. Our findings suggest that APOE's association with cognitive performance is specific to δ and partially mediated by serum inflammatory proteins. The majority of APOE's significant unadjusted effect on δ is unexplained. It may instead arise from direct central nervous system effects, possibly on native intelligence. If so, then APOE may exert a life-long influence over δ and therefore all-cause dementia risk.

Original languageEnglish (US)
Article numbere0172268
JournalPloS one
Volume12
Issue number3
DOIs
StatePublished - Mar 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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