The Association of Mid-and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study

Keenan A. Walker, B. Gwen Windham, Charles H. Brown, David S. Knopman, Clifford R. Jack, Thomas H. Mosley, Elizabeth Selvin, Dean F. Wong, Timothy M. Hughes, Yun Zhou, Alden L. Gross, Rebecca F. Gottesman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Although inflammation has been implicated in the pathogenesis of Alzheimer's disease, the effects of systemic inflammation on brain amyloid deposition remain unclear. Objective: We examined the association of midlife and late-life systemic inflammation with late-life brain amyloid levels in a community sample of non-demented older adults from the Atherosclerosis Risk in Communities (ARIC)-PET Study. Methods: 339 non-demented participants (age: 75 [SD 5]) were recruited from the ARIC Study to undergo florbetapir PET (amyloid) imaging. Blood levels of high sensitivity C-reactive protein (CRP), a marker of systemic inflammation, were measured 22 years (Visit 2), 16 years (Visit 4), and up to 2 years before PET imaging (Visit 5). Elevated brain amyloid deposition (standardized uptake value ratio >1.2) was the primary outcome. Results: Our primary analyses found no association of midlife and late-life CRP with late-life brain amyloid levels. However, in secondary stratified analyses, we found that higher midlife (Visit 2) CRP was associated with elevated amyloid among males (OR 1.65, 95% CI: 1.13-2.42), and among white (OR 1.33, 95% CI: 1.02-1.75), but not African American, participants (p-interactions<0.05). Among male participants, those who maintained high CRP levels (≥3 mg/L) throughout mid-and late-life were most likely to have elevated brain amyloid (OR, 8.81; 95% CI: 1.23, 62.91). Conclusions: Although our primary analysis does not support an association between systemic inflammation and brain amyloid deposition, we found evidence for sex-and race-dependent associations. However, findings from subgroup analyses should be interpreted with caution.

Original languageEnglish (US)
Pages (from-to)1041-1052
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2018


  • Alzheimer's disease
  • C-reactive protein
  • amyloid-beta
  • florbetapir PET
  • immune system
  • inflammation

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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