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

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 (HR=1.40; 95%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.

Metabolomic Differentials in Women With and Without Fibromyalgia

“…In this exploratory metabolomics study, untargeted (global) metabolomics analyses were performed to characterize plasma profiles of women with FM compared with women without FM with the goal of identifying differential metabolites as potential biomarkers involved with FM pathogenesis. Because of the small sample size and the cross‐sectional design of our study, we did not conduct pathway analysis but report on select metabolites that suggest a potential for clinically meaningful health consequences in persons diagnosed with FM . Study findings are intended to inform the direction for conducting future targeted metabolomic research.…”

“…The KP is understood as the primary route in the metabolism of tryptophan (Trp), an essential amino acid known to be a precursor to both serotonin and melatonin. Altered metabolism along the KP has been associated with psychiatric disorders such as depression and neurological disorders such as mild cognitive impairment and dementia . For example, in a sample of 2,067 dementia‐free Framingham Offspring Cohort participants, Chouraki et al .…”

“…Because of the small sample size and the cross-sectional design of our study, we did not conduct pathway analysis but report on select metabolites that suggest a potential for clinically meaningful health consequences in persons diagnosed with FM. 26 Study findings are intended to inform the direction for conducting future targeted metabolomic research. A number of metabolites were higher ( Table 2), and several lower, in the FM group (Table 3), relative to the comparison group.…”

“…Altered metabolism along the KP has been associated with psychiatric disorders such as depression 40 and neurological disorders such as mild cognitive impairment and dementia. 26,41 For example, in a sample of 2,067 dementia-free Framingham Offspring Cohort participants, Chouraki et al 26 reported an association between higher plasma anthranilic acid and a greater risk of dementia. Other studies have reported elevated levels of KYN 8 or lower levels of Trp 37 in persons with FM.…”

Kynurenine‐3‐monooxygenase: A new direction for the treatment in different diseases

“…However, whether it is effective or not is still unknown. KP plays an important part in neurodegenerative disorders including Alzheimer's disease (Chouraki et al, 2017;Giil et al, 2017). Studies have shown that AD patients suffered with increased tryptophan through significantly decreased KYNA (Hartai et al, 2007) and increased level of QUIN (Gulaj, Pawlak, Bien, & Pawlak, 2010).…”