Department of Biomedicine, Neuroscience and Advanced Diagnosis (BIND), University of Palermo, 90127 Palermo, Italy.
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), AOUP Paolo Giaccone, 90127 Palermo, Italy.
Int J Mol Sci. 2023 Jul 25;24(15):11922. doi: 10.3390/ijms241511922.
The inflammatory response that marks Alzheimer's disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory process which impairs β-amyloid peptide clearance capability and leads to neurotoxicity and neurodegeneration. Moreover, microglia also appear to be closely involved in the spread of tau pathology. Soluble TREM2 also represents a crucial player in the neuroinflammatory processes. Elevated levels of TREM2 in cerebrospinal fluid have been associated with increased amyloid plaque burden, neurodegeneration, and cognitive decline in individuals with Alzheimer's disease. Understanding the intricate relationship between innate immunity and Alzheimer's disease will be a promising strategy for future advancements in diagnosis and new therapeutic interventions targeting innate immunity, by modulating its activity. Still, additional and more robust studies are needed to translate these findings into effective treatments. In this review, we focus on the role of cells (microglia, astrocytes, and oligodendrocytes) and molecules (TREM2, tau, and β-amyloid) of the innate immune system in the pathogenesis of Alzheimer's disease and their possible exploitation as disease biomarkers and targets of therapeutical approaches.
阿尔茨海默病（神经炎症）的炎症反应被认为是一把双刃剑。小胶质细胞在疾病早期发挥保护作用。然而，持续的有害刺激进一步激活小胶质细胞，引发加剧的炎症过程，损害β-淀粉样肽清除能力，并导致神经毒性和神经退行性变。此外，小胶质细胞似乎也与 tau 病理学的传播密切相关。可溶性 TREM2 也是神经炎症过程中的关键参与者。脑脊液中 TREM2 水平升高与阿尔茨海默病患者的淀粉样斑块负担增加、神经退行性变和认知能力下降有关。了解先天免疫与阿尔茨海默病之间的复杂关系，将是未来在诊断和针对先天免疫的新治疗干预方面取得进展的一个有前途的策略，通过调节其活性。然而，需要更多和更强大的研究来将这些发现转化为有效的治疗方法。在这篇综述中，我们重点关注先天免疫系统中的细胞（小胶质细胞、星形胶质细胞和少突胶质细胞）和分子（TREM2、tau 和β-淀粉样蛋白）在阿尔茨海默病发病机制中的作用，以及它们作为疾病生物标志物和治疗方法靶点的可能应用。
