Microglia are the cells that comprise the innate immune system in the brain. First described more than a century ago, these cells were initially assigned a secondary role in the central nervous system (CNS) with respect to the protagonists, neurons. However, the latest advances have revealed the complexity and importance of microglia in neurodegenerative conditions such as Alzheimer’s disease (AD), the most common form of dementia associated with aging. This pathology is characterized by the accumulation of amyloid-β peptide (Aβ), which forms senile plaques in the neocortex, as well as by the aggregation of hyperphosphorylated tau protein, a process that leads to the development of neurofibrillary tangles (NFTs). Over the past few years, efforts have been focused on studying the interaction between Aβ and microglia, together with the ability of the latter to decrease the levels of this peptide. Given that most clinical trials following this strategy have failed, current endeavors focus on deciphering the molecular mechanisms that trigger the tau-induced inflammatory response of microglia. In this review, we summarize the most recent studies on the physiological and pathological functions of tau protein and microglia. In addition, we analyze the impact of microglial AD-risk genes (APOE, TREM2, and CD33) in tau pathology, and we discuss the role of extracellular soluble tau in neuroinflammation.

中文翻译：

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Tau 病理学背景下的阿尔茨海默病中的小胶质细胞

小胶质细胞是构成大脑先天免疫系统的细胞。一个多世纪前首次描述，这些细胞最初被指定在中枢神经系统 (CNS) 中相对于主角神经元发挥次要作用。然而，最新进展揭示了小胶质细胞在神经退行性疾病中的复杂性和重要性，例如阿尔茨海默病 (AD)，这是与衰老相关的最常见的痴呆形式。这种病理的特点是淀粉样蛋白 β 肽 (Aβ) 的积累，其在新皮质中形成老年斑，以及过度磷酸化的 tau 蛋白的聚集，这一过程导致神经原纤维缠结 (NFT) 的发展。在过去的几年中，人们一直致力于研究 Aβ 与小胶质细胞之间的相互作用，以及后者降低该肽水平的能力。鉴于遵循这一策略的大多数临床试验都失败了，目前的努力集中在破译触发 tau 诱导的小胶质细胞炎症反应的分子机制上。在这篇综述中，我们总结了最近关于 tau 蛋白和小胶质细胞生理和病理功能的研究。此外，我们分析了小胶质细胞 AD 风险基因的影响（APOE、TREM2和CD33 ) 在 tau 病理学中，我们讨论了细胞外可溶性 tau 在神经炎症中的作用。