Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Institute on Aging and Brain Disorders, First Affiliated Hospital of University of Science and Technology of China, Hefei, China.
Alzheimers Dement. 2021 Jul;17(7):1097-1108. doi: 10.1002/alz.12276. Epub 2021 Jan 7.
Patients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear.
We measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor β subunit (INSR-β), and soluble INSR (sINSR) levels in a clinical cohort study.
T2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR-β, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR cleavage, which was associated with insulin resistance.
The elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.
2 型糖尿病（T2DM）患者认知障碍风险较高，胰岛素抵抗起着关键作用。β-位淀粉样前体蛋白裂解酶 1（BACE1）被认为是阿尔茨海默病的预测因子。然而，BACE1 在胰岛素抵抗和 T2DM 认知障碍风险中的潜在作用尚不清楚。
我们在临床队列研究中测量了血浆 BACE1 水平、瑞典突变淀粉样前体蛋白（APPsw）和胰岛素受体β亚基（INSR-β）的 BACE1 裂解活性以及可溶性胰岛素受体（sINSR）水平。
有或没有认知障碍的 T2DM 患者表现出血浆 BACE1 水平升高，以及 APPsw 和 INSR-β 的 BACE1 酶活性升高和 sINSR 水平升高。此外，血糖状态与升高的 BACE1 水平和 BACE1 介导的 INSR 裂解相关，这与胰岛素抵抗有关。
T2DM 中升高的 BACE1 水平可能通过淀粉样蛋白生成和胰岛素抵抗增加认知障碍风险。
