Alzheimer β amyloid deposition enhanced by ApoE ε4 gene precedes neurofibrillary pathology in the frontal association cortex of nondemented senior subjects
Alzheimer β amyloid deposition enhanced by ApoE ε4 gene precedes neurofibrillary pathology in the frontal association cortex of nondemented senior subjects
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DOI：
10.1093/jnen/60.7.731
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发表时间：
2001-07-01
影响因子：
3.2
通讯作者：
Ihara, Y
中科院分区：
文献类型：
--
作者：
Yamaguchi, H;Sugihara, S;Ihara, Y
阐明阿尔茨海默病病理学如何在非痴呆受试者的大脑中发展。我们检查了 101 名年龄在 40 至 83 岁之间的患者尸检大脑额叶联合皮层中 Aβ 沉积的数量和形态、神经原纤维病理学和载脂蛋白 E (ApoE) 基因型之间的相互关系。老年斑密度与酶免疫分析 (EIA) 测量的不溶性 Aβ 的对数数据密切相关。 A beta 42- EIA 的量在临床前后期显着增加，而 A beta 42+ 斑块密度在临床前早期增加。神经原纤维病理仅出现在 A β 沉积严重的区域和 70 岁以上的受试者中。ApoE epsilon4 等位基因增强了老年受试者中的 A β 沉积。斑块相关的神经胶质 Aβ 在轻度至中度 Aβ 沉积的受试者中最为突出。脑Aβ沉积的形态从临床前早期每个斑块中含有少量Aβ的弥漫性斑块转变为临床前后期每个斑块中含有大量Aβ的原始/神经炎斑块。我们的研究结果表明，在临床前后期预防 Aβ 沉积可能是一个合理的治疗目标，特别是对于携带 ApoE epsilon4 等位基因的老年人。
To clarify how Alzheimer disease pathology develops in the brains of nondemented subjects. we examined the interrelations among the amounts and morphology of A beta deposition, neurofibrillary pathology, and apolipoprotein E (ApoE) genotype in the frontal association cortex of 101 autopsy brains from patients aged between 40 to 83. Senile plaque density correlated well with the logarithmic data of insoluble A beta measured by enzyme immunoassay (EIA). The amounts of A beta 42- EIA increased dramatically in the late preclinical stage, whereas the A beta 42+ plaque density increased in the early preclinical stage. Neurofibrillary pathology appeared only in the areas with severe A beta deposition and in subjects aged over 70. The ApoE epsilon4 allele enhanced the A beta deposition in presenile subjects. plaque-associated glial A beta was prominent in subjects with mild to moderate A beta deposition. The morphology of cerebral A beta deposition changed from diffuse plaques with small amounts of A beta in each plaque in the early preclinical stage to primitive/neuritic plaques with larger amounts of A beta in each plaque in the late preclinical stage. Our findings suggest that the prevention of A beta deposition in the late preclinical stage can be a rational therapeutic target, especially in elderly people with ApoE epsilon4 allele.