THE BIOCHEMISTRY OF BRAIN AMYLOIDS AND PREAMYLOID LESIONS

脑淀粉样变性由一组不同的疾病组成，这些疾病在 不溶物的临床表现及成分和分布 淀粉样纤维。我们认为，所有类型的大脑淀粉样蛋白都与 淀粉样前体蛋白的改变降解，以及沉积 发生在遗传或其他方面有缺陷的患者身上 这些分子。我们提出了要素的三方划分。 发病机制的中心问题：固有的化学淀粉样变 前体蛋白的潜力；异常蛋白的可能性 新陈代谢和/或遗传变异，以及疾病的存在 微环境组织因子可促进 前体蛋白转化为不溶的淀粉样蛋白产物。 最近我们发现散发性脑组织的淀粉样纤维 淀粉样血管病与常染色体显性遗传性家族性淀粉样变性 荷兰血液病患者的血管病变(也称为遗传性脑 伴有荷兰型淀粉样变性的出血)类似于阿尔茨海默病 淀粉样β蛋白(Abeta)。这些发现表明，Abeta 沉积障碍形成一系列重叠的临床病理 病情范围从以血管受累为主的患者 对于同时有血管和实质受累的患者 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”，提示 它们代表了贝塔蛋白沉积的早期阶段。类淀粉样蛋白 在神经科的患者中，有相当比例的人会出现沉积物。 无症状的老年人；因此，重要的是要澄清他们的 两性关系。 我们建议：1)生化和免疫组织化学分析 来自荷兰HCHWA患者的前叶样病变和家族性和 散发性阿尔茨海默病。2)淀粉样蛋白等的特性 家族性和散发性阿尔茨海默病的成分。3)执行类似操作 转基因小鼠的研究。这项研究对于理解 与淀粉样蛋白沉积相关的基本发病机制 衰老、淀粉样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和 治疗性干预。

Brain amyloidoses comprise a heterogeneous group of diseases that vary in clinical expression and the composition and distribution of insoluble amyloid fibrils. We believe that all types of cerebral amyloids involve altered degradation of an amyloid precursor protein, 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 amyloidogenic potential of the precursor protein; the possibility of aberrant protein metabolism and/or genetic variants, and the existence of disease microenvironmental 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 beta-protein (Abeta). These findings indicate that Abeta deposition disorders form a spectrum of overlapping clinico-pathological 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 "preamyloid lesions", suggesting that they represent an early stage of beta-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: 1) the biochemical and immunohistochemical analysis of preamyloid lesions obtained from Dutch patients with HCHWA and familial and sporadic forms of AD. 2) the characterization of amyloid protein and other components from familial and sporadic forms of AD. 3) performing similar studies in transgenic mice. 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 and for therapeutic intervention.