Davis-Salinas J, Saporito-Irwin S M, Cotman C W, Van Nostrand W E
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717-4025, USA.
J Neurochem. 1995 Aug;65(2):931-4. doi: 10.1046/j.1471-4159.1995.65020931.x.
The progression of Alzheimer's disease and related disorders involves amyloid beta-protein (A beta) deposition and pathologic changes in the parenchyma as well as 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 shown to express the A beta precursor (A beta PP) and A beta. Here, we show that A beta 1-42, an abundant cerebrovascular form of A beta, causes cellular degeneration in cultured human cerebrovascular smooth muscle cells. This stress response is accompanied by a striking increase in the levels of cellular A beta PP and soluble A beta peptide produced in these degenerating cells. These data provide the first experimental evidence that A beta can potentially contribute to the onset and progression of the cerebrovascular pathology. The present findings suggest that this mechanism may involve a molecular cascade with a novel product-precursor relationship that results in the adverse production and subsequent accumulation of A beta.
阿尔茨海默病及相关病症的进展涉及淀粉样β蛋白（Aβ）沉积以及脑实质和脑血管的病理变化。这些病症中的脑血管Aβ沉积物与血管壁中退化的平滑肌细胞相关，已证明这些平滑肌细胞表达Aβ前体（AβPP）和Aβ。在此，我们表明Aβ1-42（一种丰富的脑血管形式的Aβ）会导致培养的人脑血管平滑肌细胞发生细胞退化。这种应激反应伴随着这些退化细胞中细胞AβPP水平和可溶性Aβ肽的显著增加。这些数据提供了首个实验证据，表明Aβ可能对脑血管病理学的发生和进展有潜在作用。目前的研究结果表明，这种机制可能涉及一种具有新型产物-前体关系的分子级联反应，导致Aβ的不良产生和随后的积累。
