Relationship between apolipoprotein E and the amyloid deposits and dystrophic neurites of Alzheimer's disease
Relationship between apolipoprotein E and the amyloid deposits and dystrophic neurites of Alzheimer's disease
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DOI：
10.1111/j.1365-2990.1997.tb01325.x
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发表时间：
1997-12-01
影响因子：
5
通讯作者：
Vickers, JC
中科院分区：
文献类型：
--
作者：
Dickson, TC;Saunders, HL;Vickers, JC
虽然某些载脂蛋白E（ApoE）等位基因的遗传已被认为是阿尔茨海默病的遗传危险因素，但ApoE在该疾病的病理基础中的作用尚不清楚。一些报道强调了ApoE与β-淀粉样蛋白斑块形成或神经病理学发展的相关性。利用多标记免疫组化方法，使我们能够直接检查相对于β-淀粉样斑块，营养不良的神经突起和神经纤维缠结的ApoE免疫反应性的本地化。在阿尔茨海默病的病例中，显示高ApoE免疫反应性的β-淀粉样蛋白斑块位于新皮质的第II层、第III层和第V层。在I层中，β-淀粉样蛋白斑块未标记ApoE相对于β-淀粉样蛋白。标记为β-淀粉样蛋白的致密核心斑块通常仅具有标记为ApoE的中心部分。相反，ApoE标记的球形结构内的一些斑块不免疫反应的β-淀粉样蛋白或营养不良的神经突标记。与β-淀粉样蛋白标记斑块不同，所有ApoE免疫反应性斑块均与营养不良性神经突相关。在临床前阿尔茨海默病病例中，大多数斑块都是β-淀粉样蛋白和ApoE双标记的。ApoE没有标记营养不良的神经突或神经纤维缠结形成的早期阶段，表明ApoE可能不直接参与神经纤维病理学。痴呆患者中与营养不良性神经突相关的斑块中ApoE的特异性存在表明ApoE可能有助于更高程度的β-淀粉样蛋白原纤维形成，增强某些斑块对周围轴突造成损伤的能力。
Although the inheritance of certain apolipoprotein E (ApoE) alleles has been recognized as a genetic risk factor for Alzheimer's disease, the role of ApoE in the pathology underlying this disease is unclear. Several reports have emphasized the association of ApoE with either beta-amyloid plaque formation or the development of neurofibrillary pathology. Utilization of multiple label immunohistochemical methods enabled us to examine directly the localization of ApoE immunoreactivity relative to beta-amyloid plaques, dystrophic neurites and neurofibrillary tangles. In Alzheimer's disease cases, beta-amyloid plaques showing high ApoE immunoreactivity were localized to layers II, Ill and V of the neocortex. In layer I, beta-amyloid plaques were unlabelled for ApoE relative to beta-amyloid. Dense core plaques labelled for beta-amyloid often had only the central portions labelled for ApoE. Conversely ApoE labelled spherical structures within some plaques were not immunoreactive for beta-amyloid or dystrophic neurite markers. Unlike beta-amyloid labelled plaques, all ApoE immunoreactive plaques were associated with dystrophic neurites. In preclinical Alzheimer's disease cases, most plaques were double labelled for beta-amyloid and ApoE. ApoE did not label dystrophic neurites or the early stages of neurofibrillary tangle formation, indicating that ApoE may not be directly involved in neurofibrillary pathology. The specific presence of ApoE in plaques associated with dystrophic neurites in demented patients suggests that ApoE may contribute toward a higher degree of beta-amyloid fibrillogenesis, enhancing the ability of certain plaques to cause damage to surrounding axons.