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 journalArticlepeer-review


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
Pages (from-to)1327-1336
Number of pages10
JournalAlzheimer's and Dementia
Issue number12
StatePublished - Dec 2017

Bibliographical note

Funding Information:
This work was supported by the dedication of the Framingham Heart Study participants. This work received support from the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and HHSN268201500001I) and grants from the National Institute of Neurological Disorders and Stroke ( NS17950 ), the  National Institute on Aging ( AG008122 , AG016495 , AG049505 , AG049607 , and AG033193 ), and the National Institute of Diabetes and Digestive and Kidney Diseases ( R01-DK-HL081572 ). Role of the sponsors: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke; the National Heart, Lung, and Blood Institute; the National Institute of Aging; the National Institute of Diabetes and Digestive and Kidney Diseases; or the National Institutes of Health. The information contained in this article does not necessarily reflect the position or the policy of the US government, and no official endorsement should be inferred. Authors' contribution: V.C. and S.S helped in preparing the study design and drafting the manuscript. R.S.V. helped in study supervision and funding. Metabolites assessment was done by R.E.G. and T.J.W. Critical review of the manuscript was by all authors. Statistical methods and analysis was by S.R.P., A.B., S.L., and Q.Y.

Publisher Copyright:
© 2017 the Alzheimer's Association


  • 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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