Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Neurology, RuiJin Hospital/Lu Wan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
Neurosci Lett. 2020 Nov 1;738:135392. doi: 10.1016/j.neulet.2020.135392. Epub 2020 Sep 15.
Tumor necrosis factor-a (TNF-α) signaling pathway plays a significant role in Alzheimer's disease (AD). This study aimed to explore the relationship between TNF-α related inflammatory proteins and pathological markers of AD, and examine their possibility as a predictor of the conversion of mild cognitive impairment (MCI) to AD.
This study included both cross-sectional and longitudinal designs. The levels of TNF-α related inflammatory proteins, Aβ, total-tau(t-tau), phosphorylated tau (p-tau) from cerebrospinal fluid (CSF) were analyzed in healthy controls (HC, n = 90), MCI (n = 116), and AD participants (n = 75) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Kaplan-Meier analyses were used to evaluate the predictive value of the examined putative AD markers after follow-up visits.
In the cross-sectional cohort, we observed higher CSF levels of TNF-α related inflammatory proteins in the MCI and AD patients with positive tau pathology. TNF receptors (TNFR) were more closely associated with t-tau and p-tau than Aβ, in HC, MCI and AD subjects. In the longitudinal cohort with a mean follow-up of 30.2 months, MCI patients with high levels of CSF TNFR1 (p = 0.001) and low levels of TNFR2 (p < 0.001) were more likely to develop into AD.
TNFR-signaling might be involved in the early pathogenesis of AD and TNF receptors may serve as potential predictive biomarkers for MCI.
肿瘤坏死因子-α（TNF-α）信号通路在阿尔茨海默病（AD）中起着重要作用。本研究旨在探讨 TNF-α相关炎症蛋白与 AD 的病理标志物之间的关系，并研究它们作为轻度认知障碍（MCI）向 AD 转化的预测因子的可能性。
本研究包括横断面和纵向设计。分析了来自阿尔茨海默病神经影像学倡议（ADNI）的健康对照组（HC，n=90）、MCI 患者（n=116）和 AD 患者（n=75）的脑脊液（CSF）中 TNF-α相关炎症蛋白、Aβ、总 tau（t-tau）、磷酸化 tau（p-tau）的水平。Kaplan-Meier 分析用于评估随访后检查的潜在 AD 标志物的预测价值。
在横断面队列中，我们观察到具有阳性 tau 病理学的 MCI 和 AD 患者的 CSF 中 TNF-α相关炎症蛋白水平更高。在 HC、MCI 和 AD 受试者中，TNF 受体（TNFR）与 t-tau 和 p-tau 的相关性比 Aβ更密切。在平均随访 30.2 个月的纵向队列中，CSF TNFR1 水平高（p=0.001）和 TNFR2 水平低（p<0.001）的 MCI 患者更有可能发展为 AD。
TNFR 信号可能参与 AD 的早期发病机制，TNF 受体可能作为 MCI 的潜在预测生物标志物。
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