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14号染色体连锁的阿尔茨海默病中β淀粉样蛋白(Aβ)沉积:Aβ42(43)占主导地位

Amyloid beta protein (Abeta) deposition in chromosome 14-linked Alzheimer's disease: predominance of Abeta42(43).

作者信息

Mann D M, Iwatsubo T, Cairns N J, Lantos P L, Nochlin D, Sumi S M, Bird T D, Poorkaj P, Hardy J, Hutton M, Prihar G, Crook R, Rossor M N, Haltia M

机构信息

Department of Pathological Sciences, Division of Molecular Pathology, University of Manchester, UK.

出版信息

Ann Neurol. 1996 Aug;40(2):149-56. doi: 10.1002/ana.410400205.

Abstract

Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of 8 cases of (genetically confirmed) chromosome 14-linked Alzheimer's disease (AD) using the end-specific monoclonal antibodies BA27 and BC05 to detect the presence of Abeta40 and Abeta42(43), respectively. In all patients, Abeta42(43) was the predominant peptide species present. The total amount of Abeta40 and Abeta42(43) deposited was more than twice the amount deposited in cases of sporadic AD of similar disease duration, although the ratio between the extent of Abeta40 and Abeta42(43) deposition was unaltered, compared with sporadic AD. Therefore, (one of) the effects of the mutations in the presenilin 1:PS-1 (S182) gene may be to cause or at least promote an early and excessive deposition of Abeta42(43) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).

摘要

使用末端特异性单克隆抗体BA27和BC05,分别检测8例(经基因确认的)14号染色体连锁阿尔茨海默病(AD)患者额叶皮质中β淀粉样蛋白(Aβ)的沉积情况,以分别检测Aβ40和Aβ42(43)的存在。在所有患者中,Aβ42(43)是主要存在的肽类物质。尽管与散发性AD相比,Aβ40和Aβ42(43)沉积程度的比例未改变,但沉积的Aβ40和Aβ42(43)总量是疾病持续时间相似的散发性AD病例中沉积量的两倍多。因此,早老素1:PS-1(S182)基因突变的(其中一个)作用可能是导致或至少促进Aβ42(43)在脑内早期过度沉积,这是与其他遗传性AD形式共有的特性,如那些由淀粉样前体蛋白突变导致的AD以及唐氏综合征(21三体)。

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