Verbeek M M, Ruiter D J, de Waal R M
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Biol Chem. 1997 Sep;378(9):937-50. doi: 10.1515/bchm.1997.378.9.937.
Since the identification in 1984 of the amyloid beta protein (Abeta) as the major component of senile plaques and cerebrovascular amyloid in Alzheimer's disease (AD) brains, it is well accepted that the production of this protein is a crucial factor in the pathogenesis of AD. Abeta is produced by cleavage from the amyloid precursor protein (APP) and can form fibrils in vivo and in vitro. The formation of these fibrils is influenced by proteins that are found in association with Abeta-containing lesions in the AD brain. Several of these proteins arise by an inflammatory response of the brain to Abeta production. The distribution of different isoforms of Abeta, varying at the C-terminus of the peptide, varies among the Abeta-containing lesions in AD brains. Such variations may have consequences for the pathogenesis of AD because the various Abeta isoforms differ in their capacity to form fibrils, and they have different toxic effects on neurons and vascular cells, respectively. The experimental data indicate that the pathogenesis of senile plaques is different from the generation of cerebrovascular amyloidosis. Summarizing models for either type of AD pathology are presented.
自1984年在阿尔茨海默病（AD）患者大脑中发现β淀粉样蛋白（Aβ）是老年斑和脑血管淀粉样蛋白的主要成分以来，人们普遍认为该蛋白的产生是AD发病机制中的关键因素。Aβ由淀粉样前体蛋白（APP）裂解产生，可在体内和体外形成纤维。这些纤维的形成受AD大脑中与含Aβ病变相关的蛋白质影响。其中一些蛋白质是大脑对Aβ产生的炎症反应产生的。Aβ不同异构体在肽的C末端有所不同，其在AD大脑含Aβ病变中的分布也不同。这种差异可能对AD的发病机制产生影响，因为各种Aβ异构体形成纤维的能力不同，且它们对神经元和血管细胞分别具有不同的毒性作用。实验数据表明，老年斑的发病机制与脑血管淀粉样变性的发生不同。本文总结了这两种AD病理类型的模型。
