Harigaya Y, Saido T C, Eckman C B, Prada C M, Shoji M, Younkin S G
Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
Biochem Biophys Res Commun. 2000 Sep 24;276(2):422-7. doi: 10.1006/bbrc.2000.3490.
The amyloid beta protein (Abeta) 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 Abeta42 may be a common initiating event in all forms of AD. Here, we analyzed the amino termini of the Abeta species deposited in the AD brain, focusing specifically on species with amino-terminal pyroglutamate at position 3 (Abeta3(pE)). Immunocytochemical analysis of AD brains with an antibody specific for Abeta3(pE) confirmed that these species deposit in blood vessels and senile plaques. Using specific sandwich ELISAs, we determined the amounts of Abeta3(pE)-40 and Abeta3(pE)-42(43) in AD brain compared with other forms. This analysis showed that Abeta3(pE)-40 is closely correlated with the extent of Abeta deposition in blood vessels, whereas Abeta3(pE)-42(43) is not. In addition, Abeta3(pE)-42(43) is an important component of the Abeta deposited in senile plaques of the AD brain, constituting approximately 25% of the total Abeta42(43). In vitro comparison of Abeta1-42 and Abeta3(pE)-42 showed that Abeta3(pE)-42 is highly prone to oligomerization. These findings suggest that Abeta3(pE)-42 may be particularly important in AD pathogenesis.
沉积在阿尔茨海默病（AD）大脑中的β淀粉样蛋白（Aβ）在其氨基末端和羧基末端均具有异质性。最近对AD遗传形式的研究表明，Aβ42的聚集和沉积可能是所有形式AD的常见起始事件。在此，我们分析了沉积在AD大脑中的Aβ物种的氨基末端，特别关注在第3位具有氨基末端焦谷氨酸的物种（Aβ3（pE））。用对Aβ3（pE）特异的抗体对AD大脑进行免疫细胞化学分析证实，这些物种沉积在血管和老年斑中。使用特异性夹心ELISA，我们测定了与其他形式相比AD大脑中Aβ3（pE）-40和Aβ3（pE）-42（43）的量。该分析表明，Aβ3（pE）-40与血管中Aβ沉积的程度密切相关，而Aβ3（pE）-42（43）则不然。此外，Aβ3（pE）-42（43）是沉积在AD大脑老年斑中的Aβ的重要组成部分，约占总Aβ42（43）的25%。Aβ1-42和Aβ3（pE）-42的体外比较表明，Aβ3（pE）-42极易发生寡聚化。这些发现表明，Aβ3（pE）-42在AD发病机制中可能特别重要。
