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.
The Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Alzheimers Dement. 2017 Dec;13(12):1327-1336. doi: 10.1016/j.jalz.2017.04.009. Epub 2017 Jun 8.
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.
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.
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.
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.
与阿尔茨海默病（AD）相关的新型生物标志物的鉴定可以提供关键的生物学见解，并允许进行靶向的临床前预防。我们使用代谢组学研究了与痴呆和 AD 发病相关的循环代谢产物。
在 2067 名无痴呆的弗雷明汉后代队列参与者（平均年龄 55.9 ± 9.7 岁；52.4%为女性）中评估了 217 种代谢物的血浆水平。我们在多变量 Cox 模型中研究了它们与未来痴呆和 AD 风险的关联。
93 名参与者发生了新发痴呆（平均随访时间 15.6 ± 5.2 年）。较高的血浆氨茴酸水平与痴呆风险增加相关（危险比 [HR] = 1.40；95%置信区间 [CI] = [1.15-1.70]；P = 8.08×10）。谷氨酸（HR = 1.38；95% CI = [1.11-1.72]）、牛磺酸（HR = 0.74；95% CI = [0.60-0.92]）和次黄嘌呤（HR = 0.74；95% CI = [0.60-0.92]）水平也与痴呆风险有一定关联。
我们确定了四个具有生物学意义的候选痴呆血浆生物标志物。氨茴酸的相关性提示了色氨酸代谢途径，该途径调节谷氨酸的兴奋性毒性。与次黄嘌呤和牛磺酸的关联进一步证实了尿酸和牛磺酸可能具有神经保护作用。
