AMYLOID ANGIOPATHY, EARLY PLAQUES, AND AGING

淀粉样变性包括一组不同的疾病 在临床上的表达及其组成和分布 不溶的淀粉样蛋白纤维。据信，所有类型的 淀粉样变性涉及一种可溶性前体的过度产生，并且 沉积发生在遗传或非遗传的患者身上。 在降解这些分子方面有缺陷。我们提出了一个 三方划分对以下问题至关重要的要素 发病机制：血管内皮细胞固有的化学促淀粉样变性潜能 前体蛋白；蛋白质代谢异常的可能性， 以及疾病微环境组织因子的存在 可能会促进前体蛋白转化为其 不溶的淀粉样蛋白产品。 最近我们发现散发性的淀粉样蛋白纤维 脑淀粉样血管病与常染色体显性遗传性脑血管病 起源于荷兰的患者的家族性淀粉样血管病(也 荷兰遗传性脑出血伴淀粉样变性 类型)类似于阿尔茨海默病淀粉样蛋白B。这些 研究结果表明，B-淀粉样蛋白沉积障碍形成 重叠的临床病理情况的范围 从血管受累为主的患者到患者 具有血管和实质参与的组合 比例不一，临床表现为中风和痴呆症， 分别进行了分析。我们还发现，这些障碍表现出 不同的神经炎性斑块样结构，或“前叶样病变” 病变“表明它们代表了早期的B- 蛋白质沉积。类似的淀粉样蛋白沉积也很常见。 在神经系统无症状的老年人中，有相当比例的人 因此，重要的是澄清它们之间的关系。 我们提出如下建议：1)生化和免疫组织化学 无症状老年人和老年人早期淀粉样蛋白沉积的研究 脑淀粉样血管病患者。2)识别 老年人体内的淀粉样蛋白前体。3)元胞的研究 细胞内淀粉样蛋白前体的来源和合成 在文化中成长。 这项研究对于理解本病的基本病因具有重要意义 衰老过程中淀粉样蛋白沉积的相关机制 血管病和阿尔茨海默病；它可能对 在病理和临床水平上的诊断目的。

Amyloidosis comprises a heterogeneous group of diseases that vary in clinical expression and the composition and distribution of insoluble amyloid fibrils. It is believed that all types of amyloidosis involve overproduction of a soluble precursor, and that deposition occurs in patients who are genetically or otherwise defective in degrading these molecules. We put forward a tripartite division of the elements central to the issue of pathogenesis: the inherent chemical amyliodogenic potential of the precursor protein; the possibility of aberrant protein metabolism, and the existence of disease microenviromental tissue factors that may facilitate the conversion of precursor proteins into their insoluble amyloid products. Recently we have shown that the amyloid fibrils of sporadic cerebral amyloid angiopathy and an autosomal dominant form of familial amyloid angiopathy in patients of Dutch origin (also designated Hereditary Cerebral Hemorrhage with Amyloidosis of Dutch Type) are similar to Alzheimer Disease amyloid B-protein. These findings indicate that B-amyloid deposition disorders form a spectrum of overlapping clinicopathological conditions which range from patients with predominant vascular involvement to patients having a combination of vascular and parenchyma involvement in varying proportions, manifested clinically by stroke and dementia, respectively. We have also found that these disorders exhibit varying neuritic plaque-like structures, or "preamyloidotic lesions," suggesting that they represent an early stage of B- protein deposition. Similar amyloid deposits are often encountered in a significant percent of neurologically asymptomatic aged individuals; hence it is important to clarify their relationship. We propose the following: 1) Biochemical and immunohistochemical studies of early amyloid deposits in asymptomatic elders and patients with cerebral amyloid angiopathy. 2) Identification of the amyloid protein precursor in aged humans. 3) Study of cellular origin and synthesis of the amyloid protein precursor in cells grown in culture. This study is relevant for understanding the basic etiopathogenetic mechanisms associated with amyloid deposition in aging, amyloid angiopathy, and Alzheimer's Disease; it may be useful for diagnostic purposes at a pathological and clinical level.