Cao Wuyou, Tian Sai, Zhang Haoqiang, Zhu Wenwen, An Ke, Shi Jijing, Yuan Yang, Wang Shaohua
Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.
Medical School of Southeast University, Nanjing, China.
Front Neurosci. 2020 Sep 11;14:743. doi: 10.3389/fnins.2020.00743. eCollection 2020.
Low-density lipoprotein receptor-related protein 1 (LRP1) is involved in cerebral glucose metabolism and amyloid-β clearance. This study aimed to investigate the pathogenetic roles of LRP1 and its rs1799986 polymorphism in mild cognitive impairment (MCI) among patients with type 2 diabetes mellitus (T2DM).
A total of 166 Chinese patients with T2DM were enrolled and divided into two groups according to Montreal Cognitive Assessment (MoCA) scores. Neuropsychological tests were performed. Soluble LRP1 (sLRP1) levels were assessed using enzyme-linked immunosorbent assay, and the genotype of LRP1 rs1799986 was detected using the Sequenom method.
Diabetic patients with MCI ( = 60) exhibited significantly lower plasma sLRP1 levels ( = 0.033) and worse glucose control ( = 0.009) than the healthy cognition controls ( = 106). Multivariate regression analysis revealed plasma sLRP1 levels [odds ratio (OR) = 0.971, = 0.005] and HbA1c (OR = 1.298, = 0.003) as a risk factor for MCI in diabetic patients, in addition to insulin use and hypertension. However, there was no association between plasma sLRP1 levels and HbA1c. After adjusting for age, sex, and education level, plasma sLRP1 levels in the MCI group were negatively correlated with Stroop Color Word Test B number ( = -0.335, = 0.011), which represents selective attention, cognitive flexibility, and processing speed. Additionally, patients with T2DM carrying the T allele of LRP1 rs1799986 showed higher Auditory Verbal Learning Test (AVLT) delayed recall scores ( = 0.025).
Decreased plasma sLRP1 levels are associated with MCI, particularly with attention dysfunction, in patients with T2DM. Moreover, the T allele of LRP1 rs1799986 may decrease susceptibility to MCI. Further studies with large cohorts should be designed to elucidate the roles of LRP1 in hyperglycemia-induced cognitive decline.
低密度脂蛋白受体相关蛋白1（LRP1）参与脑葡萄糖代谢和淀粉样β蛋白清除。本研究旨在探讨LRP1及其rs1799986多态性在2型糖尿病（T2DM）患者轻度认知障碍（MCI）中的致病作用。
共纳入166例中国T2DM患者，根据蒙特利尔认知评估（MoCA）评分分为两组。进行神经心理学测试。采用酶联免疫吸附测定法评估可溶性LRP1（sLRP1）水平，采用Sequenom方法检测LRP1 rs1799986的基因型。
与健康认知对照组（n = 106）相比，MCI糖尿病患者（n = 60）的血浆sLRP1水平显著降低（P = 0.033），血糖控制更差（P = 0.009）。多因素回归分析显示，除胰岛素使用和高血压外，血浆sLRP1水平[比值比（OR）= 0.971，P = 0.005]和糖化血红蛋白（HbA1c）（OR = 1.298，P = 0.003）是糖尿病患者发生MCI的危险因素。然而，血浆sLRP1水平与HbA1c之间无关联。在调整年龄、性别和教育水平后，MCI组的血浆sLRP1水平与代表选择性注意力、认知灵活性和处理速度的Stroop色词测验B得分呈负相关（r = -0.335，P = 0.011）。此外，携带LRP1 rs1799986 T等位基因的T2DM患者的听觉词语学习测验（AVLT）延迟回忆得分更高（P = 0.025）。
血浆sLRP1水平降低与T2DM患者的MCI相关，尤其是与注意力功能障碍相关。此外，LRP1 rs1799986的T等位基因可能降低MCI的易感性。应设计更大样本量队列的进一步研究以阐明LRP1在高血糖诱导的认知衰退中的作用。
