Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD). Therefore, identifying periphery biomarkers correlated with mild cognitive impairment (MCI) is of importance for early diagnosis of AD. Here, we performed platelet proteomics in T2DM patients with MCI (T2DM-MCI) and without MCI (T2DM-nMCI). Pearson analysis of the omics data with MMSE (mini-mental state examination), Aβ1-42/Aβ1-40 (β-amyloid), and rGSK-3β(T/S9) (total to Serine-9-phosphorylated glycogen synthase kinase-3β) revealed that mitophagy/autophagy-, insulin signaling-, and glycolysis/gluconeogenesis pathways-related proteins were most significantly involved. Among them, only the increase of optineurin, an autophagy-related protein, was simultaneously correlated with the reduced MMSE score, and the increased Aβ1-42/Aβ1-40 and rGSK-3β(T/S9), and the optineurin alone could discriminate T2DM-MCI from T2DM-nMCI. Combination of the elevated platelet optineurin and rGSK-3β(T/S9) enhanced the MCI-discriminating efficiency with AUC of 0.927, specificity of 86.7%, sensitivity of 85.3%, and accuracy of 0.859, which is promising for predicting cognitive decline in T2DM patients.

中文翻译：

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识别 2 型糖尿病患者轻度认知障碍的血小板生物标志物

2 型糖尿病 (T2DM) 是阿尔茨海默病 (AD) 的独立危险因素。因此，识别与轻度认知障碍 (MCI) 相关的外围生物标志物对于 AD 的早期诊断具有重要意义。在这里，我们对患有 MCI (T2DM-MCI) 和没有 MCI (T2DM-nMCI) 的 T2DM 患者进行了血小板蛋白质组学研究。使用 MMSE（简易精神状态检查）、Aβ1-42/Aβ1-40（β-淀粉样蛋白）和 rGSK-3β(T/S9)（总到 Serine-9-磷酸化糖原合酶激酶）对组学数据进行 Pearson 分析3β) 揭示了线粒体自噬、胰岛素信号和糖酵解/糖异生途径相关蛋白的参与最为显着。其中，只有自噬相关蛋白 optineurin 的增加与 MMSE 评分降低同时相关，Aβ1-42/Aβ1-40 和 rGSK-3β(T/S9) 的增加，单独的 optineurin 可以区分 T2DM-MCI 和 T2DM-nMCI。升高的血小板 optineurin 和 rGSK-3β(T/S9) 的组合增强了 MCI 鉴别效率，AUC 为 0.927，特异性为 86.7%，敏感性为 85.3%，准确度为 0.859，有望预测 T2DM 的认知能力下降耐心。