Premium
Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study
Author(s) -
Chouraki Vincent,
Preis Sarah R.,
Yang Qiong,
Beiser Alexa,
Li Shuo,
Larson Martin G.,
Weinstein Galit,
Wang Thomas J.,
Gerszten Robert E.,
Vasan Ramachandran S.,
Seshadri Sudha
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.04.009
Subject(s) - dementia , hazard ratio , medicine , taurine , framingham heart study , uric acid , cohort , kynurenine , framingham risk score , oncology , endocrinology , disease , confidence interval , biology , biochemistry , amino acid , tryptophan
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.