Rostagno A, Tomidokoro Y, Lashley T, Ng D, Plant G, Holton J, Frangione B, Revesz T, Ghiso J
Department of Pathology, New York University School of Medicine, New York 10016, USA.
Cell Mol Life Sci. 2005 Aug;62(16):1814-25. doi: 10.1007/s00018-005-5092-5.
The importance of cerebral amyloid deposition in the mechanism of neurodegeneration is still debatable. Classic arguments are usually centered on amyloid beta(Abeta) and its role in the neuronal loss characteristic of Alzheimer's disease, the most common form of human cerebral amyloidosis. Two non-Abeta cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of Alzheimer's disease, including the presence of neurofibrillary tangles, parenchymal preamyloid and amyloid deposits, cerebral amyloid angiopathy and a variety of amyloid-associated proteins and inflammatory components. Both early-onset conditions are linked to specific mutations at or near the stop codon of the chromosome 13 gene BRI2 that cause generation of longer-than-normal protein products. Furin-like processing of these longer precursors releases two de novo-created peptides, ABri and ADan, which deposit as amyloid fibrils in FBD and FDD, respectively. Due to the similar pathology generated by completely unrelated amyloid subunits, FBD and FDD, collectively referred to as chromosome 13 dementias, constitute alternative models for studying the role of amyloid deposition in the mechanism of neuronal cell death.
脑淀粉样蛋白沉积在神经退行性变机制中的重要性仍存在争议。经典观点通常集中在β淀粉样蛋白（Aβ）及其在阿尔茨海默病（最常见的人类脑淀粉样变性形式）的神经元丢失特征中的作用。两种非Aβ脑淀粉样变性疾病，家族性英国和丹麦痴呆症（FBD和FDD），具有许多与阿尔茨海默病相同的特征，包括神经原纤维缠结、实质前淀粉样蛋白和淀粉样蛋白沉积、脑淀粉样血管病以及多种淀粉样蛋白相关蛋白和炎症成分。这两种早发性疾病都与13号染色体基因BRI2终止密码子处或附近的特定突变有关，这些突变导致产生比正常更长的蛋白质产物。这些较长前体蛋白的弗林蛋白酶样加工释放出两种新产生的肽，ABri和ADan，它们分别在FBD和FDD中沉积为淀粉样原纤维。由于完全不相关的淀粉样亚基产生了相似的病理变化，FBD和FDD统称为13号染色体痴呆症，它们构成了研究淀粉样蛋白沉积在神经元细胞死亡机制中作用的替代模型。
