Dissociation of β-Amyloid From Lipoprotein in Cerebrospinal Fluid From Alzheimer's Disease Accelerates β-Amyloid-42 Assembly
Dissociation of β-Amyloid From Lipoprotein in Cerebrospinal Fluid From Alzheimer's Disease Accelerates β-Amyloid-42 Assembly
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DOI：
10.1002/jnr.22615
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
Matsubara, Etsuro
中科院分区：
文献类型：
--
作者：
Takamura, Ayumi;Kawarabayashi, Takeshi;Matsubara, Etsuro
特异于β-淀粉样蛋白（Ab）寡聚体（A β Os）的单克隆2C 3使我们能够验证我们的假设，即中枢神经系统（CNS）中脂蛋白-A β相互作用的改变启动和/或加速有利于A β组装的级联反应。额叶皮质采用2C 3免疫沉淀明确检测可溶性4-，8-和12-聚体在阿尔茨海默病（AD）的大脑。采用2C 3的内嗅皮质的免疫印迹分析显示，可溶性12-mer的积累先于神经元损失或认知障碍的出现，并且随着Braak神经原纤维缠结（NFT）阶段的进展而增强。可溶性A β与脂蛋白颗粒的解离发生在脑脊液（CSF）中，并且无脂蛋白的寡聚体2C 3构象异构体（4- 35-mer）的存在是明显的，其模拟CNS环境。这种CNS环境可能强烈影响可溶性A β肽的构象，导致可溶性A β（42）单体转化为可溶性A β（42）组装体。研究结果表明，功能下降的脂蛋白可能会加速代谢条件的产生，导致CNS中可溶性A β（42）组装水平升高。(C)2011 Wiley-Liss，Inc.
Monoclonal 2C3 specific to beta-amyloid (Ab) oligomers (A beta Os) enabled us to test our hypothesis that the alteration of lipoprotein-A beta interaction in the central nervous system (CNS) initiates and/or accelerates the cascade favoring A beta assembly. Immunoprecipitation of frontal cortex employing 2C3 unequivocally detected soluble 4-, 8-, and 12-mers in Alzheimer's disease (AD) brains. Immunoblot analysis of the entorhinal cortex employing 2C3 revealed that the accumulation of soluble 12-mers precedes the appearance of neuronal loss or cognitive impairment and is enhanced as the Braak neurofibrially tangle (NFT) stages progress. The dissociation of soluble A beta from lipoprotein particles occurs in cerebrospinal fluid (CSF), and the presence of lipoprotein-free oligomeric 2C3 conformers (4- to 35-mers) was evident, which mimic CNS environments. Such CNS environments may strongly affect conformation of soluble A beta peptides, resulting in the conversion of soluble A beta(42) monomers into soluble A beta(42) assembly. The findings suggest that functionally declined lipoproteins may accelerate the generation of metabolic conditions leading to higher levels of soluble A beta(42) assembly in the CNS. (C) 2011 Wiley-Liss, Inc.