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Alzheimers Dement DOI:10.1016/j.jalz.2017.04.009

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

Publication TypeJournal Article
Year of Publication2017
AuthorsChouraki, V, Preis, SR, Yang, Q, Beiser, A, Li, S, Larson, MG, Weinstein, G, Wang, TJ, Gerszten, RE, Vasan, RS, Seshadri, S
JournalAlzheimers Dement
Date Published2017 Dec
KeywordsAdolescent, Adult, Aged, Alzheimer Disease, Amines, Child, Child of Impaired Parents, Child, Preschool, Cohort Studies, Dementia, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Young Adult

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). 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.


Alternate JournalAlzheimers Dement
PubMed ID28602601
PubMed Central IDPMC5722716
Grant ListR01 NS017950 / NS / NINDS NIH HHS / United States
R01 AG016495 / AG / NIA NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / WHI NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States