Nakabayashi J, Yoshimura M, Morishima-Kawashima M, Funato H, Miyakawa T, Yamazaki T, Ihara Y
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
J Neuropathol Exp Neurol. 1998 Apr;57(4):343-52. doi: 10.1097/00005072-199804000-00007.
Immunocytochemical studies clearly showed that amyloid beta-protein (A beta) deposits are widely distributed in the subcortical regions as well as the cortices of normal aged and Alzheimer disease (AD) brains. To investigate the temporal profile of A beta accumulation in the subcortical region, we quantitated A beta40 and A beta42 levels, using sensitive enzyme immunoassays, in the putamen and mammillary bodies of normal individuals aged 24 to 87 years and of AD patients. In these two regions, A beta42 was the predominant species; in particular, A beta42 was the only A beta species detected in the putamen. In several cases the mammillary body contained only A beta40, but not A beta42. Although the extent of A beta accumulation in the 2 subcortical regions was much less than that in the cortex of the same subject, A beta42 appears to accumulate in both subcortical regions at the same time as in the cortex and leptomeninges. In addition, the A beta42 levels in the putamen or in the mammillary body correlated with those in the occipitotemporal cortex. This strongly suggests that the extent of A beta42 accumulation in the brain is determined not only by the duration of A beta accumulation but also by other unknown regional factors. Western blotting showed that the initial A beta species to accumulate in the putamen or mammillary body varied among individuals. In some cases, an A beta42 stable dimer was the most predominant species, while in other cases a 3 or 4 kD A beta42 monomer was more abundant, suggesting that the clearance rates of the A beta42 stable dimer and monomer are different in vivo.
免疫细胞化学研究清楚地表明，β-淀粉样蛋白（Aβ）沉积物广泛分布于正常老年和阿尔茨海默病（AD）脑的皮质下区域以及皮质中。为了研究皮质下区域Aβ积累的时间特征，我们使用灵敏的酶免疫测定法，对24至87岁的正常个体以及AD患者的壳核和乳头体中的Aβ40和Aβ42水平进行了定量。在这两个区域中，Aβ42是主要类型；特别是，Aβ42是壳核中检测到的唯一Aβ类型。在一些病例中，乳头体仅含有Aβ40，而不含有Aβ42。尽管这两个皮质下区域的Aβ积累程度远低于同一受试者皮质中的积累程度，但Aβ42似乎在皮质下区域和皮质及软脑膜中同时积累。此外，壳核或乳头体中的Aβ42水平与枕颞叶皮质中的水平相关。这强烈表明，脑中Aβ42的积累程度不仅取决于Aβ积累的持续时间，还取决于其他未知的区域因素。蛋白质印迹法显示，壳核或乳头体中最初积累的Aβ类型在个体之间存在差异。在某些情况下，Aβ42稳定二聚体是最主要的类型，而在其他情况下，3或4 kD的Aβ42单体更为丰富，这表明Aβ42稳定二聚体和单体在体内的清除率不同。
