Department of Biology, University of Virginia, Charlottesville, VA, USA.
Prion. 2013 Jan-Feb;7(1):14-9. doi: 10.4161/pri.22118. Epub 2012 Sep 10.
Alzheimer disease (AD) has traditionally been thought to involve the misfolding and aggregation of two different factors that contribute in parallel to pathogenesis: amyloid-β (Aβ) peptides, which represent proteolytic fragments of the transmembrane amyloid precursor protein, and tau, which normally functions as a neuronally enriched, microtubule-associated protein that predominantly accumulates in axons. Recent evidence has challenged this model, however, by revealing numerous functional interactions between Aβ and tau in the context of pathogenic mechanisms for AD. Moreover, the propagation of toxic, misfolded Aβ and tau bears a striking resemblance to the propagation of toxic, misfolded forms of the canonical prion protein, PrP, and misfolded Aβ has been shown to induce tau misfolding in vitro through direct, intermolecular interaction. In this review we discuss evidence for the prion-like properties of both Aβ and tau individually, as well as the intriguing possibility that misfolded Aβ acts as a template for tau misfolding in vivo.
阿尔茨海默病（AD）传统上被认为涉及两种不同因素的错误折叠和聚集，它们平行地促进发病机制：淀粉样β（Aβ）肽，代表跨膜淀粉样前体蛋白的蛋白水解片段，和tau，其正常功能为富含神经元的微管相关蛋白，主要在轴突中积累。然而，最近的证据通过揭示 AD 发病机制中 Aβ 和 tau 之间的许多功能相互作用对该模型提出了挑战。此外，有毒的、错误折叠的 Aβ 和 tau 的传播与有毒的、错误折叠的典型朊病毒蛋白 PrP 的传播惊人地相似，并且已经证明错误折叠的 Aβ 通过直接的、分子间相互作用在体外诱导 tau 的错误折叠。在这篇综述中，我们讨论了 Aβ 和 tau 各自具有类朊病毒特性的证据，以及错误折叠的 Aβ 作为体内 tau 错误折叠模板的有趣可能性。
