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

Affiliations

¹ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA; Lille University, Inserm, Lille University Hospital, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases, Labex Distalz, Lille, France. Electronic address: vchourak@bu.edu.
² The Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ School of Public Health, University of Haifa, Israel.
⁵ The Framingham Heart Study, Framingham, MA, USA; Division of Cardiovascular Medicine, Vanderbilt Heart & Vascular Institute, Nashville, TN, USA.
⁶ Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ The Framingham Heart Study, Framingham, MA, USA; Department of Medicine (Sections of Preventive Medicine and Cardiology), Boston University School of Medicine, Boston, MA, USA.
⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA. Electronic address: suseshad@bu.edu.

PMID: 28602601
PMCID: PMC5722716
DOI: 10.1016/j.jalz.2017.04.009

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

Vincent Chouraki et al. Alzheimers Dement. 2017 Dec.

. 2017 Dec;13(12):1327-1336.

doi: 10.1016/j.jalz.2017.04.009. Epub 2017 Jun 8.

Authors

Affiliations

¹ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA; Lille University, Inserm, Lille University Hospital, Institut Pasteur de Lille, U1167 - RID-AGE - Risk factors and molecular determinants of aging-related diseases, Labex Distalz, Lille, France. Electronic address: vchourak@bu.edu.
² The Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ School of Public Health, University of Haifa, Israel.
⁵ The Framingham Heart Study, Framingham, MA, USA; Division of Cardiovascular Medicine, Vanderbilt Heart & Vascular Institute, Nashville, TN, USA.
⁶ Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ The Framingham Heart Study, Framingham, MA, USA; Department of Medicine (Sections of Preventive Medicine and Cardiology), Boston University School of Medicine, Boston, MA, USA.
⁸ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA. Electronic address: suseshad@bu.edu.

PMID: 28602601
PMCID: PMC5722716
DOI: 10.1016/j.jalz.2017.04.009

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.

Keywords: Alzheimer's disease; Anthranilic acid; Cohort studies; Dementia; Epidemiology; Glutamic acid; Hypoxanthine; Kynurenines; Metabolomics; Plasma biomarkers; Taurine; Uric acid.

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Figures

**Figure 1**
Manhattan Plot of the Associations with Risk of Incident Dementia across the Three Sets of Metabolites in the Framingham Offspring Cohort. NOTES. P-values are represented on the y-axis after -log10 transformation; thus the higher a dot is, the lower the p-value. Metabolites are represented on the x-axis, grouped by categories. The plain line represents the significance threshold of 1.35x10⁻³ calculated in this study. The dotted line represents a suggestive threshold of 10⁻².

**Figure 2**
Kaplan-Meier curves of survival without dementia according to quartiles of anthranilic acid

See this image and copyright information in PMC

References

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

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

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Conflict of interest statement

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