van Duinen S G, Castaño E M, Prelli F, Bots G T, Luyendijk W, Frangione B
Proc Natl Acad Sci U S A. 1987 Aug;84(16):5991-4. doi: 10.1073/pnas.84.16.5991.
Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related beta-protein. Silver stain-positive, "senile plaque-like" structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approximately equal to 4000 and its partial amino acid sequence to position 21 showed homology to the beta-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of beta-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.
荷兰患者的遗传性脑出血伴淀粉样变性是一种常染色体显性血管淀粉样变性，局限于软脑膜和大脑皮层。临床上，该疾病的特征是脑出血导致早期死亡。对5例患者的免疫组织化学研究显示，血管淀粉样沉积物与针对与阿尔茨海默病相关的β蛋白同源的合成肽产生的抗血清发生强烈反应。抗血清也标记了银染阳性的“老年斑样”结构，但这些病变缺乏阿尔茨海默病典型斑块中存在的致密淀粉样核心。未发现神经原纤维缠结。从一名临床上无痴呆迹象的患者的软脑膜血管中纯化出淀粉样原纤维。该蛋白的分子量约为4000，其至第21位的部分氨基酸序列与阿尔茨海默病和唐氏综合征的β蛋白具有同源性。这些结果表明，荷兰型遗传性脑出血伴淀粉样变性在发病机制上与阿尔茨海默病相关，并支持这样一种概念，即该疾病中最初的淀粉样沉积发生在血管壁，然后才损害脑实质。因此，β蛋白在脑组织中的沉积似乎与一系列涉及血管综合征、进行性痴呆或两者兼有的疾病有关。
