Ohm T G, Kirca M, Bohl J, Scharnagl H, Gross W, März W
Zentrum der Morphologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Neuroscience. 1995 Jun;66(3):583-7. doi: 10.1016/0306-4522(94)00596-w.
Only recently, evidence was provided that apolipoprotein E allele epsilon 4 located on Chromosome 19 is associated with late onset (i.e. senile) sporadic Alzheimer's disease. Histologically, Alzheimer's disease is associated with intraneuronal neurofibrillary changes and extraneuronal A4/beta-amyloid deposition. We set out with a histological staging system which considers the gradual development of Alzheimer's disease-related histological changes over time and correlates highly with the cognitive decline ante mortem. Our analysis revealed that both the mean stage for A4/beta-amyloid deposits and the mean stage for neurofibrillary tangles get significantly shifted upwards in epsilon 4-carriers. This represents an earlier onset of the histopathological process of about one decade. The fact that both types of Alzheimer's disease-related changes correlate positively with the prevalence of the epsilon 4-allele suggests for a causal relationship between the apolipoprotein E polymorphism and the development of Alzheimer's disease.
直到最近，才有证据表明位于19号染色体上的载脂蛋白Eε4等位基因与晚发型（即老年性）散发性阿尔茨海默病有关。从组织学上看，阿尔茨海默病与神经元内神经原纤维变化和神经元外A4/β-淀粉样蛋白沉积有关。我们采用了一种组织学分期系统，该系统考虑了阿尔茨海默病相关组织学变化随时间的逐渐发展，并且与生前认知能力下降高度相关。我们的分析显示，在ε4携带者中，A4/β-淀粉样蛋白沉积的平均分期和神经原纤维缠结的平均分期都显著向上偏移。这意味着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都与ε4等位基因的患病率呈正相关，这一事实表明载脂蛋白E多态性与阿尔茨海默病的发展之间存在因果关系。
