Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
The Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Mol Neurodegener. 2022 Aug 19;17(1):53. doi: 10.1186/s13024-022-00559-3.
The Amyloid theory of Alzheimer's disease (AD) suggests that the deposition of Amyloid β (Aβ) in the brain triggers a chain of events, involving the deposition of phosphorylated Tau and other misfolded proteins, leading to neurodegeneration via neuroinflammation, oxidative stress, and neurovascular factors. The infectious theory linked various infectious agents with the development of AD, raising the possibility that they serve as etiological causes of the disease. Are these theories mutually exclusive, or do they coincide?
In this review, we will discuss how the two theories converge. We present a model by which (1) the systemic infectious burden accelerates the development of AD brain pathology via bacterial Amyloids and other pathogen-associated molecular patterns (PAMPs), and (2) the developing AD brain pathology increases its susceptibility to the neurotoxicity of infectious agents -derived PAMPs, which drive neurodegeneration via activated microglia.
The reciprocal effects of amyloid deposition and systemic infectious burden may lead to a vicious cycle fueling Alzheimer's disease pathogenesis.
阿尔茨海默病（AD）的淀粉样蛋白理论表明，大脑中淀粉样蛋白β（Aβ）的沉积引发了一系列事件，涉及磷酸化 Tau 和其他错误折叠蛋白的沉积，通过神经炎症、氧化应激和神经血管因素导致神经退行性变。传染性理论将各种传染性病原体与 AD 的发展联系起来，提出了它们可能是该疾病病因的可能性。这些理论是否相互排斥，还是它们一致？
在这篇综述中，我们将讨论这两种理论是如何趋同的。我们提出了一个模型，其中（1）系统传染性负担通过细菌淀粉样蛋白和其他病原体相关分子模式（PAMPs）加速 AD 大脑病理的发展，以及（2）正在发展的 AD 大脑病理增加了其对传染性病原体衍生的 PAMPs 的神经毒性的易感性，通过激活的小胶质细胞驱动神经退行性变。
淀粉样蛋白沉积和系统传染性负担的相互影响可能导致恶性循环，加剧阿尔茨海默病的发病机制。
