A MUTATION IN THE AMYLOID PRECURSOR PROTEIN ASSOCIATED WITH HEREDITARY ALZHEIMERS-DISEASE
A MUTATION IN THE AMYLOID PRECURSOR PROTEIN ASSOCIATED WITH HEREDITARY ALZHEIMERS-DISEASE
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DOI：
10.1126/science.1925564
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发表时间：
1991-10-04
期刊：
影响因子：
56.9
通讯作者：
BENSON, MD
中科院分区：
文献类型：
--
作者：
MURRELL, J;FARLOW, M;BENSON, MD
阿尔茨海默病是一种局部淀粉样变性，其特征在于大脑皮质淀粉样斑块、神经纤维缠结和软脑膜血管壁内的淀粉样沉积物。 虽然大多数阿尔茨海默病病例是散发性的，但该综合征的常染色体显性遗传的运动性提示单个突变可能在发病机制中很重要。 对一个经尸检证实的阿尔茨海默病家族的DNA进行直接测序，发现淀粉样前体蛋白的跨膜结构域中有一个氨基酸取代（苯丙氨酸取代瓦尔）。 该突变与本研究中所有患者中阿尔茨海默病的存在相关，并且可能是导致淀粉样纤维形成和痴呆的遗传因素。
Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of leptomeningeal vessels. Although most cases of Alzheimer's disease are sporadic, kindreds with autosomal-dominant inheritance of the syndrome suggest that a single mutation may be important in pathogenesis. Direct sequencing of DNA from a family with autopsy-proven Alzheimer's disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and may be the inherited factor causing both amyloid fibril formation and dementia.