A seed for Alzheimer amyloid in the brain
A seed for Alzheimer amyloid in the brain
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DOI：
10.1523/jneurosci.0861-04.2004
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发表时间：
2004-05-19
影响因子：
5.3
通讯作者：
Yanagisawa, K
中科院分区：
文献类型：
--
作者：
Hayashi, H;Kimura, N;Yanagisawa, K
关于阿尔茨海默病（AD）的早期发病机制的一个基本问题涉及淀粉样β蛋白（Abeta）的毒性聚集体是如何从其无毒的可溶形式形成的。我们先前假设GM1神经节苷脂结合的Abeta（GAbeta）参与了这一过程。我们现在使用从AD脑中纯化的针对GA β的新型单克隆抗体来研究这种可能性。在这里，我们报告，GAbeta具有不同于可溶性Abeta的构象，并作为种子启动Abeta聚集。此外，通过免疫组织化学和免疫沉淀研究验证了大脑中GA β的产生。这些结果暗示了AD发病的潜在机制，并表明内源性种子可以成为治疗策略的靶点。
A fundamental question about the early pathogenesis of Alzheimer's disease (AD) concerns how toxic aggregates of amyloid beta protein (Abeta) are formed from its nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound Abeta (GAbeta) is involved in the process. We now examined this possibility using a novel monoclonal antibody raised against GAbeta purified from an AD brain. Here, we report that GAbeta has a conformation distinct from that of soluble Abeta and initiates Abeta aggregation by acting as a seed. Furthermore, GAbeta generation in the brain was validated by both immunohistochemical and immunoprecipitation studies. These results imply a mechanism underlying the onset of AD and suggest that an endogenous seed can be a target of therapeutic strategy.