We recently reported accelerated cognitive decline in Europeans aged > 70 years with low circulating adropin levels. Adropin is a small, secreted peptide that is highly expressed in the human nervous system. Expression profiling indicate relationships between adropin expression in the human brain and pathways that affect dementia risk. Moreover, increased adropin expression or treatment using synthetic adropin improves cognition in mouse models of aging. Here we report that low circulating adropin concentrations associate with poor cognition (worst quintile for a composite score derived from the MMSE and semantic fluency test) in late-middle aged community-dwelling African Americans (OR = 0.775, P < 0.05; age range 45–65 y, n = 352). The binomial logistic regression controlled for sex, age, education, cardiometabolic disease risk indicators, and obesity. Previous studies using cultured cells from the brains of human donors suggest high expression in astrocytes. In snRNA-seq data from the middle temporal gyrus (MTG) of human donors, adropin expression is higher in astrocytes relative to other cell types. Adropin expression in all cell-types declines with advance age, but is not affected by dementia status. In cultured human astrocytes, adropin expression also declines with donor age. Additional analysis indicated positive correlations between adropin and transcriptomic signatures of energy metabolism and protein synthesis that are adversely affected by donor age. Adropin expression is also suppressed by pro-inflammatory factors. Collectively, these data indicate low circulating adropin levels are a potential early risk indicator of cognitive impairment. Declining adropin expression in the brain is a plausible link between aging, neuroinflammation, and risk of cognitive decline.

我们最近报告称，70 岁以上的欧洲人的认知能力加速下降，循环阿德洛品水平较低。Adropin 是一种小型分泌肽，在人类神经系统中高度表达。表达谱表明人脑中的 adropin 表达与影响痴呆风险的途径之间的关系。此外，增加adropin表达或使用合成adropin治疗可改善小鼠衰老模型的认知能力。在这里，我们报告说，低循环阿德罗品浓度与居住在社区的中老年非裔美国人的认知能力差（MMSE 和语义流畅性测试得出的综合得分最差五分位数）相关（OR = 0.775，P < 0.05；年龄 范围 45 –65 y，n  = 352）。二项逻辑回归控制了性别、年龄、教育程度、心脏代谢疾病风险指标和肥胖。先前使用人类捐赠者大脑培养细胞进行的研究表明，星形胶质细胞中存在高表达。在人类捐赠者颞中回 (MTG) 的 snRNA-seq 数据中，星形胶质细胞中的 adropin 表达相对于其他细胞类型更高。所有细胞类型中的 Adropin 表达都会随着年龄的增长而下降，但不受痴呆状态的影响。在培养的人星形胶质细胞中，adropin 表达也会随着供体年龄的增长而下降。进一步的分析表明，adropin 与能量代谢和蛋白质合成的转录组特征之间存在正相关性，而这些特征受到供体年龄的不利影响。Adropin 表达也受到促炎因子的抑制。总的来说，这些数据表明低循环阿德洛品水平是认知障碍的潜在早期风险指标。大脑中 adropin 表达的下降可能是衰老、神经炎症和认知能力下降风险之间的联系。