阿尔茨海默病患者脑脊液中tau蛋白、β淀粉样蛋白1-40及β淀粉样蛋白1-42（43）水平的纵向研究：一项日本的研究

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

作者信息

Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, Sasaki H, Abe K, Iwatsubo T, Kosaka T, Watanabe M, Tomidokoro Y, Shizuka M, Mizushima K, Nakamura T, Igeta Y, Ikeda Y, Amari M, Kawarabayashi T, Ishiguro K, Harigaya Y, Wakabayashi K, Okamoto K, Hirai S, Shoji M

机构信息

Department of Neurology, Gunma University School of Medicine, Japan.

出版信息

Ann Neurol. 1998 Jul;44(1):17-26. doi: 10.1002/ana.410440108.

DOI:10.1002/ana.410440108

PMID:9667589

Abstract

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

摘要

为阐明伴随正常衰老及阿尔茨海默病（AD）进展过程中脑脊液（CSF）中tau蛋白、淀粉样β蛋白（Aβ）1-40和Aβ1-42（43）的变化情况，采用灵敏的酶联免疫吸附测定法，对来自三个独立机构的93例AD患者、这93例AD患者中的32例纵向研究对象、33例非AD痴呆患者、56例其他神经系统疾病患者及54例正常对照者的CSF样本进行了分析。尽管tau水平随衰老而升高，但在AD患者中观察到tau显著升高且tau水平与临床进展之间存在相关性。在AD患者中观察到Aβ1-42（43）水平显著降低以及Aβ1-40与Aβ1-42（43）的比率显著升高。纵向AD研究显示，在AD发病前Aβ1-42（43）水平持续较低且Aβ1-40与Aβ1-42（43）的比率升高。这些发现表明，CSF tau可能随痴呆的临床进展而增加，并且CSF中Aβ1-42（43）水平及Aβ1-40与Aβ1-42（43）的比率变化可能在AD的早期阶段就已开始。通过检测CSF tau、Aβ1-40和Aβ1-42（43），利用tau水平及Aβ1-40与Aβ1-42（43）的比率，提供了有效的诊断敏感性（71%）和特异性（83%），并且在纵向评估中敏感性提高到了91%。