Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada.
Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada.
Neurosci Biobehav Rev. 2020 May;112:1-27. doi: 10.1016/j.neubiorev.2020.01.026. Epub 2020 Jan 26.
Alzheimer's disease (AD) is characterized neuropathologically by progressive neurodegeneration and by the presence of amyloid plaques and neurofibrillary tangles. These plaques and tangles are composed, respectively, of amyloid-beta (Aβ) and tau proteins. While long recognized as hallmarks of AD, it remains unclear what causes the formation of these insoluble deposits. One theory holds that prion-like templated misfolding of Aβ and tau induces these proteins to form pathological aggregates, and propagation of this misfolding causes the stereotyped progression of pathology commonly seen in AD. Supporting this theory, numerous studies have been conducted in which aggregated Aβ, tau, or α-synuclein is injected intracerebrally into pathology-free host animals, resulting in robust formation of pathology. Here, we review this literature, focusing on in vivo intracerebral seeding of Aβ and tau in mice. We compare the results of these experiments to what is known about the seeding and spread of α-synuclein pathology, and we discuss how this research informs our understanding of the factors underlying the onset, progression, and outcomes of proteinaceous pathologies.
阿尔茨海默病（AD）的神经病理学特征是进行性神经退行性变，以及淀粉样斑块和神经纤维缠结的存在。这些斑块和缠结分别由淀粉样β（Aβ）和tau 蛋白组成。虽然淀粉样蛋白斑块和神经纤维缠结长期以来被认为是 AD 的标志，但导致这些不溶性沉积物形成的确切原因仍不清楚。一种理论认为，淀粉样蛋白β（Aβ）和 tau 的类朊病毒样模板错误折叠诱导这些蛋白形成病理性聚集，并且这种错误折叠的传播导致 AD 中常见的刻板的病理进展。支持这一理论，已经进行了许多研究，其中将聚集的 Aβ、tau 或 α-突触核蛋白脑内注射到无病理宿主动物中，导致病理的大量形成。在这里，我们回顾了这方面的文献，重点关注 Aβ和 tau 在小鼠中的体内脑内播种。我们将这些实验的结果与已知的 α-突触核蛋白病理的播种和传播进行了比较，并讨论了这些研究如何告知我们对蛋白病理基础、发病、进展和结果的因素的理解。
