Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain
Amyloid β protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain
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DOI：
10.1006/bbrc.2000.3490
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发表时间：
2000-09-24
影响因子：
3.1
通讯作者：
Younkin, SG
中科院分区：
文献类型：
--
作者：
Harigaya, Y;Saido, TC;Younkin, SG
沉积在阿尔茨海默病（AD）大脑中的β淀粉样蛋白（A β）在其氨基端和羧基端都是异质的。最近对阿尔茨海默病遗传形式的研究表明，A β 42的聚集和沉积可能是所有形式阿尔茨海默病的共同起始事件。在这里，我们分析了沉积在AD大脑中的A β物种的氨基末端，特别关注氨基末端焦谷氨酸位于3位（A β 3(pE)）的物种。用A β 3（pE）特异性抗体对AD脑进行免疫细胞化学分析，证实这些物质沉积在血管和老年斑中。使用特异性夹心elisa，我们测定了A β 3(pE)-40和A β 3(pE)-42（43）在AD大脑中的含量，并与其他形式进行了比较。结果表明，A β 3(pE)-40与A β在血管中的沉积程度密切相关，而A β 3(pE)-42（43）与此无关。此外，A β 3(pE)-42（43）是沉积在AD脑老年斑中的A β的重要组成部分，约占A β 42总量的25%（43）。A β 1-42和A β 3(pE)-42的体外比较表明，A β 3(pE)-42极易发生寡聚化。这些发现表明A β 3(pE)-42可能在AD发病机制中特别重要。(C) 2000年学术出版社。
The amyloid beta protein (A beta) deposited in the Alzheimer's disease (AD) brain is heterogeneous at both its amino and carboxyl termini. Recent studies of the genetic forms of AD indicate that the aggregation and deposition of A beta 42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the A beta species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (A beta 3(pE)). Immunocytochemical analysis of AD brains with an antibody specific for A beta 3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of A beta 3(pE)-40 and A beta 3(pE)-42(43) in AD brain compared with other forms. This analysis showed that A beta 3(pE)-40 is closely correlated with the extent of A beta deposition in blood vessels, whereas A beta 3(pE)-42(43) is not. In addition, A beta 3(pE)-42(43) is an important component of the A beta deposited in senile plaques of the AD brain, constituting approximately 25% of the total A beta 42(43). In vitro comparison of A beta 1-42 and A beta 3(pE)-42 showed that A beta 3(pE)-42 is highly prone to oligomerization. These findings suggest that A beta 3(pE)-42 may be particularly important in AD pathogenesis. (C) 2000 Academic Press.