März W, Scharnagl H, Kirça M, Bohl J, Gross W, Ohm T G
Department of Medicine, Albert Ludwigs-University, Freiburg, Germany.
Ann N Y Acad Sci. 1996 Jan 17;777:276-80. doi: 10.1111/j.1749-6632.1996.tb34432.x.
Recent work provided evidence that the apolipoprotein (apo) E polymorphism is associated with late-onset sporadic Alzheimer's disease. The major histological hallmarks of Alzheimer's disease are the extraneuronal deposition of A4/beta-amyloid and the intraneuronal formation of neurofibrillary tangles, the latter correlating strongly with the psychometric status. We examined the relationship between the apo E polymorphism and Alzheimer's disease-related histological changes using a staging system which accounts for the progression of the disease over time and correlates well with the cognitive decline ante mortem. We observed a significant positive correlation between both neurofibrillary changes and A4/beta-amyloid deposits and the epsilon 4 gene dose. We estimated that the presence of one apo E4 allele leads to an earlier onset of the histopathological process of about one decade. The association of both types of Alzheimer's disease-related changes with the prevalence of the epsilon 4-allele suggests that the apo E polymorphism causally contributes to the development of Alzheimer's disease.
最近的研究提供了证据，表明载脂蛋白（apo）E多态性与晚发性散发性阿尔茨海默病相关。阿尔茨海默病的主要组织学特征是A4/β-淀粉样蛋白的细胞外沉积和神经原纤维缠结的细胞内形成，后者与心理测量状态密切相关。我们使用一种分期系统来研究apo E多态性与阿尔茨海默病相关组织学变化之间的关系，该系统考虑了疾病随时间的进展，并且与生前认知能力下降密切相关。我们观察到神经原纤维变化和A4/β-淀粉样蛋白沉积与ε4基因剂量之间存在显著正相关。我们估计，一个apo E4等位基因的存在会导致组织病理学过程提前约十年开始。两种类型的阿尔茨海默病相关变化与ε4等位基因的患病率之间的关联表明，apo E多态性在因果关系上促成了阿尔茨海默病的发展。
