Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.
Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.
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DOI：
10.1073/pnas.84.16.5991
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发表时间：
1987-08
影响因子：
11.1
通讯作者：
S. V. Duinen;E. M. Castaño;F. Prelli;G. Bots;W. Luyendijk;B. Frangione
中科院分区：
文献类型：
--
作者：
S. V. Duinen;E. M. Castaño;F. Prelli;G. Bots;W. Luyendijk;B. Frangione
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形式的血管淀粉样变性，局限于软脑膜和大脑皮质。临床上该病以脑损害为主要特征，可导致早期死亡。对5名患者的免疫组织化学研究显示，血管淀粉样蛋白沉积物与针对与阿尔茨海默病相关β蛋白同源的合成肽的抗血清发生强烈反应。银染阳性的“老年斑样”结构也被抗血清标记，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蛋白核心。不存在神经纤维缠结。从一名临床上没有痴呆症状的患者的软脑膜血管中纯化淀粉样原纤维。该蛋白质的分子量约等于4000，其至位置21的部分氨基酸序列显示与阿尔茨海默病和唐氏综合征的β-蛋白质同源。这些结果表明，遗传性脑出血与淀粉样变性的荷兰起源是发病相关的阿尔茨海默病和支持的概念，在这种疾病的初始淀粉样蛋白沉积发生在血管壁损伤脑实质之前。因此，脑组织中β蛋白的沉积似乎与血管综合征、进行性痴呆或两者兼而有之的一系列疾病有关。
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.