Murrell J, Farlow M, Ghetti B, Benson M D
Indiana University School of Medicine, Department of Medicine.
Science. 1991 Oct 4;254(5028):97-9. doi: 10.1126/science.1925564.
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.
阿尔茨海默病是一种局限性淀粉样变性病，其特征为大脑皮质淀粉样斑块、神经原纤维缠结以及软脑膜血管壁内的淀粉样沉积物。尽管大多数阿尔茨海默病病例为散发性，但该综合征具有常染色体显性遗传特征的家族表明，单个突变可能在发病机制中起重要作用。对一个经尸检证实患有阿尔茨海默病的家族的DNA进行直接测序，结果显示淀粉样前体蛋白跨膜结构域中有一个单氨基酸替代（苯丙氨酸替代缬氨酸）。该突变与本研究中所有患者的阿尔茨海默病存在相关，可能是导致淀粉样原纤维形成和痴呆的遗传因素。
