Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

背景：β-Site APP 裂解酶 1 (BACE1) 是参与 2 型糖尿病 (T2DM) 和轻度认知障碍 (MCI) 病理生理学的关键酶。我们旨在研究血浆 BACE1 水平和 BACE1 基因多态性与 MCI 的 T2DM 患者不同认知表现的潜在关联。

方法：根据蒙特利尔认知评估 (MoCA) 评分，将招募的 186 名 T2DM 受试者分为 92 名 MCI 组和 94 名健康认知对照组。评估了社会人口学特征、临床参数和神经心理学测试。测定了 BACE1 C786G 基因多态性和血浆 BACE1 水平。

结果：与对照组相比，MCI 患者表现出更高的血浆 BACE1 水平。在调整空腹血糖、糖化血红蛋白和体内平衡后，血浆 BACE1 水平与 MoCA、时钟绘图测试和逻辑记忆测试分数呈负相关，而与 MCI 组的 Trail Making Test-B 时间呈正相关（均 p<0.05） C肽对胰岛素抵抗的模型评估。多变量逻辑回归分析显示，T2DM 患者血浆 BACE1 水平高时 MCI 风险增加的显着趋势（OR = 1.492，p = 0.027）。T2DM-MCI患者GG和GC基因型血浆BACE1水平明显高于CC基因型（分别为p=0.035；p=0.026）。

结论：血浆 BACE1 水平升高与 T2DM-MCI 患者的整体认知功能较差有关，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 MCI 的危险因素，可能受 BACE1 C786G 基因突变的影响。