PNAS：β-淀粉样蛋白致阿尔茨海默氏症新机制

近日，来自美国加州大学的研究人员发现，一种储存在人类大脑中被认为调控阿尔茨海默氏病发作的肽类物质就像朊病毒一样的方式发挥作用，朊病毒是以通过哺乳动物神经组织传播方式发挥作用的。这篇最新论文发表在PNAS杂志上，研究人员证实β-淀粉样肽（Aβ）会像朊病毒传播方式那样聚集到脑组织引起的疾病。

朊病毒就是蛋白质病毒，是只有蛋白质而没有核酸的病毒。朊病毒是一类能引起哺乳动物和人的中枢神经系统病变的传染性的病变因子，它们引起的疾病是传染病如疯牛病。朊病毒对人类最大的威胁是可以导致人类和家畜患中枢神经系统退化性病变，最终不治而亡。

这项新的研究中，科研人员使用荧光分子标记β-淀粉样蛋白后导入小鼠大脑中，然后观察近一年时间里小鼠大脑里发生的事件。由于带有荧光分子，研究人员能够跟踪肽的位置，结果发现β-淀粉样蛋白会传播到大脑的另一侧，最终破坏​​整个大脑结构。这表明Aβ或许与朊病毒类似，是一个可怕的东西。但β-淀粉样蛋白会不会像朊病毒那样具有传染性，迄今还没有任何研究证实。

doi:10.1073/pnas.1206555109
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Purified and synthetic Alzheimer’s amyloid beta (Aβ) prions

Jan Sthra, Joel C. Wattsa, Zachary L. Mensinger, Abby Oehlerc, Sunny K. Grilloa, Stephen J. DeArmonda, Stanley B. Prusinera, and Kurt Gilesa

The aggregation and deposition of amyloid-β (Aβ) peptides are believed to be central events in the pathogenesis of Alzheimer’s disease (AD). Inoculation of brain homogenates containing Aβ aggregates into susceptible transgenic mice accelerated Aβ deposition, suggesting that Aβ aggregates are capable of self-propagation and hence might be prions. Recently, we demonstrated that Aβ deposition can be monitored in live mice using bioluminescence imaging (BLI). Here, we use BLI to probe the ability of Aβ aggregates to self-propagate following inoculation into bigenic mice. We report compelling evidence that Aβ aggregates are prions by demonstrating widespread cerebral β-amyloidosis induced by inoculation of either purified Aβ aggregates derived from brain or aggregates composed of synthetic Aβ. Although synthetic Aβ aggregates were sufficient to induce Aβ deposition in vivo, they exhibited lower specific biological activity compared with brain-derived Aβ aggregates. Our results create an experimental paradigm that should lead to identification of self-propagating Aβ conformations, which could represent novel targets for interrupting the spread of Aβ deposition in AD patients.