Ebrahimi Rasoul, Shahrokhi Nejad Shahrzad, Falah Tafti Mahdi, Karimi Zahra, Sadr Seyyedeh Reyhaneh, Ramadhan Hussein Dana, Talebian Niki, Esmaeilpour Khadijeh
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Metab Brain Dis. 2025 May 17;40(5):207. doi: 10.1007/s11011-025-01631-9.
Microglial activation has emerged as a hallmark of neuroinflammation in Alzheimer's disease (AD). Central to this process is the formation and accumulation of amyloid beta (Aβ) peptide and neurofibrillary tangles, both of which contribute to synaptic dysfunction and neuronal cell death. Aβ oligomers trigger microglial activation, leading to the release of pro-inflammatory cytokines, which further exacerbates neuroinflammation and neuronal damage. Importantly, the presence of activated microglia surrounding amyloid plaques is correlated with heightened production of cytokines such as interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), creating a vicious cycle of inflammation. While microglia play a protective role by clearing Aβ plaques during the early stages of AD, their chronic activation can lead to detrimental outcomes, including enhanced tau pathology and neuronal apoptosis. Recent studies have highlighted the dualistic nature of microglial activation, showcasing both inflammatory (M1) and anti-inflammatory (M2) phenotypes that fluctuate based on the surrounding microenvironment. Disruption in microglial function and regulation can lead to neurovascular dysfunction, further contributing to the cognitive decline seen in AD. Moreover, emerging biomarkers and imaging techniques are unveiling the complexity of microglial responses in AD, providing avenues for targeted therapeutics aimed at modulating these cells. Understanding the intricate interplay between microglia, Aβ, and tau pathology is vital for developing potential interventions to mitigate neuroinflammation and its impact on cognitive decline in AD. This review synthesizes current findings regarding microglial activation and its implications for AD pathogenesis, offering insights into future therapeutic strategies.
小胶质细胞激活已成为阿尔茨海默病（AD）神经炎症的一个标志。这一过程的核心是β淀粉样蛋白（Aβ）肽的形成和积累以及神经原纤维缠结，二者都会导致突触功能障碍和神经元细胞死亡。Aβ寡聚体触发小胶质细胞激活，导致促炎细胞因子的释放，这进一步加剧了神经炎症和神经元损伤。重要的是，淀粉样斑块周围活化小胶质细胞的存在与白细胞介素（IL）-1β和肿瘤坏死因子-α（TNF-α）等细胞因子的产生增加相关，从而形成炎症的恶性循环。虽然小胶质细胞在AD早期通过清除Aβ斑块发挥保护作用，但其慢性激活会导致有害后果，包括tau病理增加和神经元凋亡。最近的研究强调了小胶质细胞激活的二元性，展示了基于周围微环境而波动的炎性（M1）和抗炎（M2）表型。小胶质细胞功能和调节的破坏会导致神经血管功能障碍，进一步促使AD中出现认知衰退。此外，新出现的生物标志物和成像技术正在揭示AD中小胶质细胞反应的复杂性，为旨在调节这些细胞的靶向治疗提供了途径。了解小胶质细胞、Aβ和tau病理之间复杂的相互作用对于开发潜在干预措施以减轻神经炎症及其对AD认知衰退的影响至关重要。本综述综合了关于小胶质细胞激活及其对AD发病机制影响的当前研究结果，为未来的治疗策略提供了见解。
