The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the brain‐resident macrophages, known as microglia, and their receptors as integral regulators of both the initiation and propagation of inflammation, Aβ accumulation, neuronal loss, and memory decline in AD. Emerging studies have also begun to reveal critical roles for distinct innate immune pathways in AD pathogenesis, which has led to great interest in harnessing the innate immune response as a therapeutic strategy to treat AD. In this review, we will highlight recent advancements in our understanding of innate immunity and inflammation in AD onset and progression. Additionally, there has been mounting evidence suggesting pivotal contributions of environmental factors and lifestyle choices in AD pathogenesis. Therefore, we will also discuss recent findings, suggesting that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.

中文翻译：

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先天免疫在阿尔茨海默病中的作用。


近 30 年来，淀粉样蛋白假说一直主导阿尔茨海默病 (AD) 研究。这一假说取决于β淀粉样蛋白（Aβ）肽在AD中神经原纤维缠结（NFT）传播和最终认知障碍中的主要临床作用。 AD 领域的最新研究发现，大脑中的巨噬细胞（称​​为小胶质细胞）及其受体是 AD 中炎症的发生和传播、Aβ 积累、神经元丢失和记忆力下降的整体调节因子。新兴研究也开始揭示独特的先天免疫途径在 AD 发病机制中的关键作用，这引起了人们对利用先天免疫反应作为治疗 AD 的治疗策略的极大兴趣。在这篇综述中，我们将重点介绍我们对 AD 发病和进展中先天免疫和炎症的理解的最新进展。此外，越来越多的证据表明环境因素和生活方式选择在 AD 发病机制中发挥着关键作用。因此，我们还将讨论最近的发现，表明许多 AD 危险因素通过调节小胶质细胞和免疫反应影响 AD 进展。