Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study

Vincent Chouraki, Sarah R. Preis, Qiong Yang, Alexa Beiser, Shuo Li, Martin G. Larson, Galit Weinstein, Thomas J. Wang, Robert E. Gerszten, Ramachandran S. Vasan, Sudha Seshadri

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Introduction: The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics. Methods: Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models. Results: Ninety-three participants developed incident dementia (mean follow-up = 15.6 ± 5.2 years). Higher plasma anthranilic acid levels were associated with greater risk of dementia (hazard ratio [HR] = 1.40; 95% confidence interval [CI] = [1.15–1.70]; P = 8.08 × 10−4). Glutamic acid (HR = 1.38; 95% CI = [1.11–1.72]), taurine (HR = 0.74; 95% CI = [0.60–0.92]), and hypoxanthine (HR = 0.74; 95% CI = [0.60–0.92]) levels also showed suggestive associations with dementia risk. Discussion: We identified four biologically plausible, candidate plasma biomarkers for dementia. Association of anthranilic acid implicates the kynurenine pathway, which modulates glutamate excitotoxicity. The associations with hypoxanthine and taurine strengthen evidence that uric acid and taurine may be neuroprotective.

Original languageEnglish (US)
Pages (from-to)1327-1336
Number of pages10
JournalAlzheimer's and Dementia
Volume13
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Anthranilic acid
  • Cohort studies
  • Dementia
  • Epidemiology
  • Glutamic acid
  • Hypoxanthine
  • Kynurenines
  • Metabolomics
  • Plasma biomarkers
  • Taurine
  • Uric acid

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    Chouraki, V., Preis, S. R., Yang, Q., Beiser, A., Li, S., Larson, M. G., Weinstein, G., Wang, T. J., Gerszten, R. E., Vasan, R. S., & Seshadri, S. (2017). Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study. Alzheimer's and Dementia, 13(12), 1327-1336. https://doi.org/10.1016/j.jalz.2017.04.009