Association of amine biomarkers with incident dementia and Alzheimer's disease in the Framingham Study
| Autor: | Martin G. Larson, Qiong Yang, Galit Weinstein, Vincent Chouraki, Shuo Li, Alexa S. Beiser, Robert E. Gerszten, Sudha Seshadri, Thomas J. Wang, Ramachandran S. Vasan, Sarah R. Preis |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Pathology Taurine Kynurenine pathway Adolescent Epidemiology Kaplan-Meier Estimate Article Cohort Studies Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Framingham Heart Study Child of Impaired Parents Developmental Neuroscience Alzheimer Disease Internal medicine medicine Humans Dementia Amines Child Aged Framingham Risk Score Proportional hazards model business.industry Health Policy Hazard ratio Middle Aged medicine.disease Psychiatry and Mental health 030104 developmental biology chemistry Child Preschool Uric acid Female Neurology (clinical) Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's & Dementia. 13:1327-1336 |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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