Funato H, Yoshimura M, Kusui K, Tamaoka A, Ishikawa K, Ohkoshi N, Namekata K, Okeda R, Ihara Y
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
Am J Pathol. 1998 Jun;152(6):1633-40.
In this study we sought to learn about when and how amyloid beta-protein (A beta) accumulates in the cortex of normal individuals and about the difference in the A beta accumulation between normal aged and Alzheimer's disease (AD) brains. From consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal cortex T4 were sampled for A beta quantitation by the well characterized two-site enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42 accumulation between the ages of 50 and 70 years in T4 and a little later in CA1. The A beta 42 levels were consistently higher in T4 than those in CA1 in any given case. The levels of A beta 42 in AD brains were significantly higher than those in control brains, and the extent of A beta 42 amino-terminal modification was also much greater in AD brains than that in control brains. Even in cases in which no senile plaques were immunocytochemically detected, EIAs clearly showed that significant amounts of A beta 42 already had accumulated. In contrast to A beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high levels were found to be associated with AD.
在本研究中,我们试图了解β淀粉样蛋白(Aβ)在正常个体皮质中何时以及如何积累,以及正常老年人与阿尔茨海默病(AD)脑之间Aβ积累的差异。从连续的尸检病例和AD病例中,采集海马CA1区和枕颞叶皮质T4区样本,通过特征明确的双位点酶免疫测定法(EIA)对Aβ进行定量分析。在T4区,50至70岁之间有强烈的Aβ42积累趋势,在CA1区则稍晚一些。在任何给定病例中,T4区的Aβ42水平始终高于CA1区。AD脑中的Aβ42水平显著高于对照脑,且AD脑中Aβ42氨基末端修饰的程度也远大于对照脑。即使在免疫细胞化学检测未发现老年斑的病例中,EIA也清楚地显示已经积累了大量的Aβ42。与Aβ42相反,Aβ40没有明显的年龄依赖性积累,且发现其高水平与AD相关。