Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pathophysiology, School of Basic Medicine, Ministry of Education Key Laboratory for Neurological Disorders, Hubei Key Laboratory for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Alzheimers Dis. 2024;100(s1):S115-S129. doi: 10.3233/JAD-240455.
The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD.
To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline.
A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-β level, platelet GSK-3β activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure.
Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3β activity, and higher plasma Aβ42/Aβ40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3β activity was negatively correlated with brain structures.
Elevated platelet GSK-3β activity and plasma Aβ42/Aβ40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.
阿尔茨海默病（AD）的患病率正在增加，因此，确定能够预测易患 AD 的生物标志物至关重要。2 型糖尿病（T2D）是 AD 的独立危险因素。早期预测可能更容易患 AD 的 T2D 患者，从而实现早期干预，对于降低 AD 的患病率具有重要意义。
建立可预测 T2D 转化为 AD 样认知衰退的外周生物标志物。
对 159 例 T2D 患者进行了一项随访研究。采用逻辑回归分析认知状态（以 MMSE 评分表示）与多外周生物标志物（包括 APOE 基因型、血浆淀粉样蛋白-β水平、血小板 GSK-3β活性和嗅觉评分）之间的相关性。ROC 曲线用于建立预测模型。此外，对 38 例 T2D 患者进行 MRI 检查，以分析认知功能、生物标志物和脑结构之间的相关性。
与在随访期间保持正常认知功能的患者相比，发生 MCI 的患者嗅觉功能更差，血小板 GSK-3β活性更高，血浆 Aβ42/Aβ40 比值更高。我们建立了一个预测模型，表明 T2D 患者更有可能发生 AD 样认知衰退。MRI 数据显示 MMSE 评分与脑结构呈正相关。然而，血小板 GSK-3β 活性与脑结构呈负相关。
血小板 GSK-3β 活性升高和 Aβ42/Aβ40 比值降低伴嗅觉功能减退与 T2D 患者的 AD 样认知衰退相关，可用于预测哪些 T2D 患者会在极早期转化为 AD 样认知衰退。
