Ozawa K, Tomiyama T, Maat-Schieman M L, Roos R A, Mori H
Department of Neuroscience, Institute of Gerontology, Osaka City University, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Ann N Y Acad Sci. 2002 Nov;977:149-54. doi: 10.1111/j.1749-6632.2002.tb04810.x.
Cerebrovascular deposition of the amyloid beta-protein (Abeta) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders. Such an Abeta vascular deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses, including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Abeta deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. We analyzed cerebral Abeta deposition in brains with AD and Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) on the basis of two amyloid species of Abeta(40) and Abeta(42/43) using specific monoclonal antibodies. Compared to Abeta deposition in senile plaques, the molecular composition of Abeta was distinguishable, indicating that the Abeta(40) species is the main component for vascular amyloid. Furthermore, we found Abeta(42/43) immunoreactivity was also much increased in amyloid angiopathy of all cases with HCHWA-D. Taken together, amyloid angiopathy in HCHWA-D may share an Abeta(42)-driven deposition mechanism with plaque amyloid, resulting in enhanced Abeta(40) deposition.
淀粉样β蛋白（Aβ）在脑血管中的沉积是阿尔茨海默病（AD）及某些相关疾病患者常见的病理事件。这种Aβ血管沉积主要以组装的纤维状状态出现在脑血管壁的中层。这些沉积物与多种病理反应相关，包括脑血管壁平滑肌细胞的变性。严重的脑血管Aβ沉积病例还伴有血管壁完整性丧失和出血性中风。尽管这种病理后果的原因尚不清楚，但脑血管壁内蛋白水解机制的改变可能与之有关。我们使用特异性单克隆抗体，基于Aβ（40）和Aβ（42/43）这两种淀粉样蛋白，分析了AD和荷兰型遗传性脑出血伴淀粉样变性（HCHWA-D）患者大脑中的脑Aβ沉积情况。与老年斑中的Aβ沉积相比，Aβ的分子组成是可区分的，这表明Aβ（40）是血管淀粉样蛋白的主要成分。此外，我们发现所有HCHWA-D病例的淀粉样血管病中，Aβ（42/43）的免疫反应性也显著增加。综上所述，HCHWA-D中的淀粉样血管病可能与斑块淀粉样蛋白共享一种由Aβ（42）驱动的沉积机制，从而导致Aβ（40）沉积增加。
