国际神经病学神经外科学杂志2024,Vol.51Issue(4):23-27,5.DOI:10.16636/j.cnki.jinn.1673-2642.2024.04.004
血浆中tau蛋白磷酸化表达在多奈哌齐治疗阿尔茨海默病中的机制研究
Mechanism of the expression of phosphorylated tau protein in plasma in the treatment of Alzheimer's disease with donepezil
摘要
Abstract
Objective To investigate the protective mechanism of donepezil against Alzheimer's disease(AD)based on tau protein phosphorylation in plasma.Methods From January 2019 to July 2022,the samples of two groups of participants were collected from Department of Neurology,The First Hospital of Qiqihar.The first group of samples were collected from 58 patients with mild to severe AD and 20 healthy elderly controls,while the other group of samples were collected from 37 patients with mild to moderate AD,among whom 18 patients received donepezil treatment for 24 weeks and 19 patients received placebo treatment for 24 weeks.Extracellular vesicles(EVs)derived from neurons were extracted from the blood samples of the patients,and ELISA kits were used to measure the levels of β-amyloid 42(Aβ42),P-T181-tau,P-S396-tau,t-tau,and NRGN.Results Compared with the control group,the patients with AD had significant increases in the levels of Aβ42,t-tau,P-T181-tau,and P-S396-tau(P<0.05)and a significant reduction in the level of NRGN in EVs(P<0.05).In the patients with AD,the levels of t-tau,NRGN,and REST in EVs were negatively correlated with the scores of Mini-Mental State Examination and Alzheimer's Disease Cooperative Study-Activity of Daily Living(P<0.05)and was positively correlated with the score of Alzheimer's Disease Assessment Scale-cognitive subscale(P<0.05).During the 24-week treatment,compared with the placebo group,the donepezil group showed significant reductions in the levels of Aβ42,t-tau,P-T181-tau,and P-S396-tau in EVs from baseline to week 24(P<0.05).Conclusions There are increases in the levels of Aβ42,t-tau,P-T181-tau,and P-S393-tau in plasma EVs of patients with mild to moderate AD,and the increases in the levels of t-tau,NRGN,and REST may be associated with the decline in cognitive function and activities of daily living.Donepezil treatment can reduce the expression levels of t-tau,P-T181-tau,and P-S396-tau in patients with mild to moderate AD.关键词
阿尔茨海默病/tau蛋白/磷酸化/多奈哌齐/神经元衍生的细胞外囊泡Key words
Alzheimer's disease/tau protein/phosphorylation/donepezil/extracellular vesicles derived from neurons分类
医药卫生引用本文复制引用
付晶,张成发,安春贺,吴诗卉,于慧..血浆中tau蛋白磷酸化表达在多奈哌齐治疗阿尔茨海默病中的机制研究[J].国际神经病学神经外科学杂志,2024,51(4):23-27,5.基金项目
黑龙江省卫生健康委员会科研课题(ZYW2021-561). (ZYW2021-561)