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散发性阿尔茨海默病中的载脂蛋白E:等位基因变异与受体相互作用

Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions.

作者信息

Rebeck G W, Reiter J S, Strickland D K, Hyman B T

机构信息

Department of Neurology, Massachusetts General Hospital, Boston 02114.

出版信息

Neuron. 1993 Oct;11(4):575-80. doi: 10.1016/0896-6273(93)90070-8.

Abstract

An increased prevalence of apolipoprotein E (ApoE) epsilon 4 allele exists in late onset familial Alzheimer's disease. We found, in sporadic Alzheimer's disease, that 62% of patients possessed an ApoE-epsilon 4 allele, compared with 20% of controls. ApoE-epsilon 4/4 patients had more senile plaques (SPs) than epsilon 3/3 patients. ApoE immunoreactivity of SPs was equivalent in both groups. Two receptors bind ApoE complexes, the low density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP). In normal brain, anti-LRP antibodies strongly stained neurons and lightly stained astrocytes; anti-LDL receptor antibodies stained only the neuropil and astrocytes. In Alzheimer's disease, SPs and reactive astrocytes were also strongly LRP immunoreactive. Colocalization of ApoE and LRP to SPs implies that these molecules may be involved in metabolism of components of SPs.

摘要

载脂蛋白E(ApoE)ε4等位基因在晚发型家族性阿尔茨海默病中的患病率增加。我们发现,在散发性阿尔茨海默病中,62%的患者拥有ApoE-ε4等位基因,而对照组为20%。ApoE-ε4/4患者比ε3/3患者有更多的老年斑(SPs)。两组中SPs的ApoE免疫反应性相当。有两种受体可结合ApoE复合物,即低密度脂蛋白(LDL)受体和LDL受体相关蛋白(LRP)。在正常大脑中,抗LRP抗体强烈染色神经元,轻度染色星形胶质细胞;抗LDL受体抗体仅染色神经纤维网和星形胶质细胞。在阿尔茨海默病中,SPs和反应性星形胶质细胞也有强烈的LRP免疫反应性。ApoE和LRP在SPs处的共定位意味着这些分子可能参与SPs成分的代谢。

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