Lu Yanhui, Jiang Xinjun, Liu Shuling, Li Mingzi
School of Nursing, Peking University Health Science Center, Beijing, China.
Front Aging Neurosci. 2018 Oct 11;10:271. doi: 10.3389/fnagi.2018.00271. eCollection 2018.
Increased risks for Alzheimer's disease (AD) are a well-recognized consequence of diabetes, insulin resistance (IR), and hyperinsulinemia. Since cerebrospinal fluid (CSF) is surrounding the central nervous system, alterations of β-amyloid (Aβ) and tau protein in the CSF may be indicative of AD-type degenerations in the brain. Current laboratory diagnosis of AD uses three biomarkers in CSF: Aβ1-42, total tau (t-Tau), and phosphorylated tau (p-Tau). However, changes in these biomarkers in diabetic and prediabetic patients are scattered and variable in literature. Thus, we attempt to perform a systematical analysis of these available data. MEDLINE, EMBASE, the Cochrane Central database, China National Knowledge Infrastructure (CNKI), and Wanfang Data electronic databases were searched to gather published studies that have evaluated the AD-type biomarkers in the CSF of subjects with diabetes, IR, or hyperinsulinemia in comparison with respective controls. Overall analysis of the published data showed no significant differences in Aβ1-42, t-Tau, and p-Tau levels in the CSF between the (pre)diabetic subjects and controls. However, subgroup analysis suggested that (pre)diabetic conditions might accelerate decrease of Aβ1-42, but increase of t-Tau levels in the CSF of subjects with cognitive impairment, and the association with p-Tau in the CSF was stronger ( = 0.001) for diabetes than those of prediabetes ( = 0.61). Our analyses reveal that the relationship between (pre)diabetic conditions and AD-type biomarker status in the CSF was subjective to clinical characteristics.
阿尔茨海默病（AD）风险增加是糖尿病、胰岛素抵抗（IR）和高胰岛素血症的一个公认后果。由于脑脊液（CSF）环绕着中枢神经系统，CSF中β-淀粉样蛋白（Aβ）和tau蛋白的改变可能表明大脑中存在AD型退变。目前AD的实验室诊断使用CSF中的三种生物标志物：Aβ1-42、总tau蛋白（t-Tau）和磷酸化tau蛋白（p-Tau）。然而，糖尿病和糖尿病前期患者中这些生物标志物的变化在文献中是分散且多变的。因此，我们试图对这些现有数据进行系统分析。检索了MEDLINE、EMBASE、Cochrane中心数据库、中国知网（CNKI）和万方数据电子数据库，以收集已发表的研究，这些研究评估了糖尿病、IR或高胰岛素血症患者CSF中AD型生物标志物，并与各自的对照组进行了比较。对已发表数据的总体分析表明，糖尿病前期患者与对照组CSF中Aβ1-42、t-Tau和p-Tau水平无显著差异。然而，亚组分析表明，糖尿病前期状态可能会加速认知功能受损患者CSF中Aβ1-42的降低，但会增加t-Tau水平，并且糖尿病患者CSF中与p-Tau的关联（P = 0.001）比糖尿病前期患者（P = 0.61）更强。我们的分析表明，糖尿病前期状态与CSF中AD型生物标志物状态之间的关系取决于临床特征。
