Tian Sai, Huang Rong, Guo Dan, Lin Hongyan, Wang Jiaqi, An Ke, Wang Shaohua
Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing, China.
School of Medicine, Southeast University, Nanjing, China.
Curr Alzheimer Res. 2020;17(4):355-364. doi: 10.2174/1567205017666200522210957.
β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI.
The recruited 186 T2DM subjects were divided into 92 MCI group and 94 healthy-cognition controls, according to the Montreal Cognitive Assessment (MoCA) scores. Sociodemographic characteristics, clinical parameters and neuropsychological tests were assessed. BACE1 C786G gene polymorphism and plasma BACE1 level were determined.
Compared to controls, MCI patients exhibited higher plasma BACE1 levels. Plasma BACE1 levels were negatively associated with MoCA, Clock Drawing Test and Logical Memory Test scores, whereas positively associated with Trail Making Test-B time in the MCI group (all p<0.05), after adjusting fasting blood glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance by C-peptide. Multivariable logistic regression analysis showed a significant trend towards increased MCI risk with high plasma BACE1 level in T2DM patients (OR = 1.492, p = 0.027). The plasma BACE1 levels of GG and GC genotypes were obviously higher than that of CC genotype in T2DM-MCI patients (p = 0.035; p = 0.026, respectively).
Increased plasma BACE1 levels were associated with poor overall cognition functions, especially visuospatial abilities, visual/logical memory and executive functions in T2DM-MCI patients. Additionally, elevated plasma BACE1 level was a risk factor for MCI in T2DM patients, and might be influenced by BACE1 C786G gene mutations.
β-淀粉样前体蛋白裂解酶1（BACE1）是参与2型糖尿病（T2DM）和轻度认知障碍（MCI）病理生理过程的关键酶。我们旨在研究T2DM合并MCI患者血浆BACE1水平和BACE1基因多态性与不同认知表现之间的潜在关联。
根据蒙特利尔认知评估（MoCA）评分，将招募的186例T2DM受试者分为92例MCI组和94例健康认知对照组。评估社会人口学特征、临床参数和神经心理学测试。测定BACE1 C786G基因多态性和血浆BACE1水平。
与对照组相比，MCI患者血浆BACE1水平较高。在调整空腹血糖、糖化血红蛋白和通过C肽进行的胰岛素抵抗稳态模型评估后，MCI组血浆BACE1水平与MoCA、画钟试验和逻辑记忆测试得分呈负相关，而与连线试验B时间呈正相关（均p<0.05）。多变量逻辑回归分析显示，T2DM患者血浆BACE1水平升高时MCI风险有显著增加趋势（OR = 1.492，p = 0.027）。T2DM-MCI患者中GG和GC基因型的血浆BACE1水平明显高于CC基因型（分别为p = 0.035；p = 0.026）。
血浆BACE1水平升高与T2DM-MCI患者整体认知功能差有关，尤其是视觉空间能力、视觉/逻辑记忆和执行功能。此外，血浆BACE1水平升高是T2DM患者发生MCI的危险因素，可能受BACE1 C786G基因突变影响。
