阿尔茨海默病患者的脑脊液tau蛋白及Aβ1-42水平

摘要

目的 探讨脑脊液(cerebrospinal fluid,CSF)中tau蛋白及β-淀粉样蛋白1-42(Aβ1-42)对诊断阿尔茨海默病(Alzheimer's disease,AD)的早期诊断价值,寻找AD理想的生物学标志.方法 采用酶联免疫吸附法检测36例AD、24例血管性痴呆患者(vascular dementia,VD)和26名正常对照者(对照组)CSF中tau蛋白及Aβ1-42浓度的变化.结果 CSF中tau蛋白平均浓度:AD组(336±126)ng/L,VD组(183±96)ng/L,对照组(98±54)ng/L,AD组CSF中tau蛋白浓度明显高于对照组,差异有统计学意义(P<0.05);CSF中Aβ1-42平均浓度:AD组(341β113)ng/L,VD组(457±132)ng/L,对照组(502±167)ng/L,AD组CSF中Aβ1-42浓度明显低于对照组.差异有显著性意义(P<0.05).结论 脑脊液Aβ1-42、tau蛋白浓度的变化,不仅对诊断阿尔茨海默病具有较高的敏感性和特异性,而且亦可作为阿尔茨海默病与血管性痴呆鉴别诊断的生物学指标.%Objective To investigate the relationship between impaired hippocampal neurogenesis and altered Notchl signaling in depressed rats. Methods In the present study, chronic unpredictable mild stress (CUMS) was used to inhibit the neurogenesis in the hippocampus. The function of Notchl signaling was investigated by using realtime PCR and western blot at different time points (14 d and 28 d) during chronic stress. The hippocampal neurogenesis was monitored by assessing cell proliferation, survival, and differentiation. Results After 14 days, CUMS significantly reduced weight (P < 0.05), the sucrose preference (P < 0.001), number of squares crossed (P < 0.01) and number of grooming and rearing compared with the controls. The immobility time was significantly increased after 14 d CUMS treated relative to the controls (P < 0.001). Twenty-eight days after CUMS protocol, these parameters were significantly difference in rats exposed to CUMS compare with the controls (weight, P < 0.05; sucrose preference, P < 0.001; number of squares crossed, P< 0.001; number of grooming and rearing, P < 0.001; and immobility time, P < 0.001). During stress, the cell proliferation and survival in DG were decreased compared with the control (P < 0.001). The mRNA and protein levels of Notchl signaling components (NICD, Hes 1, Hes 5, Jag 1) in the hippocampus decreased during stress (P < 0.001). Conclusions These results suggest that chronic stress reduce Notchl signaling function in the hippocampus and the down-regulation of the Notchl pathway caused by chronic stress might partly contribute to decreased neurogenesis in the hippocampus.