Department of Neurology and Center for Neurodegenerative Diseases, School of Medicine, Emory University, Atlanta, GA, USA.
Rutgers Robert Wood Johnson Medical School and Rutgers Institute for Health, Health Care Policy and Aging Research, Rutgers Biomedical and Health Sciences, New Brunswick, NJ, USA.
Nat Commun. 2021 Jun 28;12(1):4001. doi: 10.1038/s41467-021-24220-7.
Neuroinflammation is associated with Alzheimer's disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer's Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer's disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer's disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer's markers.
神经炎症与阿尔茨海默病有关，但脑脊液炎症蛋白测量的应用可能受到重叠途径和它们之间关系的限制。在这项工作中，我们测量了 15 种与小胶质细胞和 T 细胞功能相关的脑脊液蛋白，并在来自阿尔茨海默病神经影像学倡议的 382 名参与者以及来自两个独立队列的参与者中，证明它们在诊断类别内和跨诊断类别可重现地形成功能相关的组。我们进一步表明，与可溶性肿瘤坏死因子受体 1 相关的蛋白质水平较高与多中心（p=0.027）和独立（p=0.038）因预测的阿尔茨海默病导致轻度认知障碍人群向痴呆转化的风险降低相关，而可溶性 TREM2 水平较高与阿尔茨海默病痴呆阶段的下降速度较慢相关。因此，这些炎症蛋白提供了与既定阿尔茨海默病标志物无关的预后信息。
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