Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host
Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host
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DOI：
10.1126/science.1131864
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发表时间：
2006-09-22
期刊：
影响因子：
56.9
通讯作者：
Jucker, Mathias
中科院分区：
文献类型：
--
作者：
Meyer-Luehmann, Melanie;Coomaraswamy, Janaky;Jucker, Mathias
蛋白质聚集是阿尔茨海默病中一种已确定的致病机制，但对于这一过程在体内是如何起始的却知之甚少。向脑内注射来自阿尔茨海默病患者或β - 淀粉样前体蛋白（APP）转基因小鼠的含稀释的β - 淀粉样蛋白（Aβ）的脑提取物，以时间和浓度依赖的方式在APP转基因小鼠中诱导了脑β - 淀粉样病变及相关病理改变。脑提取物的接种活性可因Aβ免疫清除、蛋白质变性或宿主的Aβ免疫而降低或消除。外源性诱导的淀粉样病变的表型取决于宿主和致病因子的来源，这表明存在具有不同生物学活性的多态性Aβ毒株，类似于朊病毒毒株。
Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (A beta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by A beta immunodepletion, protein denaturation, or by A beta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic A beta strains with varying biological activities reminiscent of prion strains.