Van Nostrand W E, Davis-Salinas J, Saporito-Irwin S M
Department of Microbiology, College of Medicine, University of California, Irvine 92717-4025, USA.
Ann N Y Acad Sci. 1996 Jan 17;777:297-302. doi: 10.1111/j.1749-6632.1996.tb34436.x.
One of the hallmark pathologic characteristics of Alzheimer's disease (AD) and related disorders is deposition of the 39-42 amino acid amyloid beta-protein (A beta) in the walls of cerebral blood vessels. The cerebrovascular A beta deposits in these disorders are associated with degenerating smooth muscle cells in the vessel wall which have been implicated in the expression of the amyloid beta-protein precursor (A beta PP) and formation of A beta. We have established primary cultures of human cerebrovascular smooth muscle cells as a model for investigating the cellular pathologic processes involved in the cerebral amyloid angiopathy of AD and related disorders. Recently, we have shown that A beta 1-42, the predominant pathologic cerebrovascular form of A beta, causes extensive cellular degeneration that is accompanied by a striking increase in the levels of cellular A beta PP, potentially amyloidogenic carboxyl terminal A beta PP fragments, and soluble A beta peptide in the cultured human cerebrovascular smooth muscle cells. Together, these studies provide evidence that A beta contributes to the onset and progression of the cerebrovascular pathology associated with AD and related disorders and suggests the mechanism involves a molecular cascade with a novel product-precursor relationship that results in the adverse production and accumulation of A beta.
阿尔茨海默病（AD）及相关疾病的标志性病理特征之一是39 - 42个氨基酸的β-淀粉样蛋白（Aβ）沉积于脑血管壁。这些疾病中的脑血管Aβ沉积物与血管壁中退化的平滑肌细胞有关，而这些平滑肌细胞与淀粉样β蛋白前体（AβPP）的表达及Aβ的形成有关。我们已经建立了人脑血管平滑肌细胞的原代培养体系，以此作为研究AD及相关疾病脑淀粉样血管病中细胞病理过程的模型。最近，我们发现，Aβ的主要病理性脑血管形式Aβ1 - 42会导致广泛的细胞退化，同时伴随着培养的人脑血管平滑肌细胞中细胞AβPP、潜在的淀粉样生成性羧基末端AβPP片段以及可溶性Aβ肽水平的显著增加。这些研究共同提供了证据，表明Aβ促成了与AD及相关疾病相关的脑血管病理的发生和发展，并提示其机制涉及一个具有新的产物-前体关系的分子级联反应，该反应导致Aβ的不良产生和积累。
