Microglia play a critical role in Alzheimer's disease (AD) pathogenesis. They are the resident immune cells of the central nervous system (CNS) and are involved in maintaining brain homeostasis, clearing debris, and responding to pathogens. In AD, microglia become activated and aggregate around amyloid plaques, which are extracellular deposits of β-amyloid (Aβ) peptides. Human genetic studies have shown that many AD risk genes are highly expressed by microglia, suggesting their involvement in AD pathogenesis. These genes include TREM2, which is essential for microglial function and is associated with AD risk. Mutations in TREM2, such as R47H, impair microglial activation and contribute to AD progression. Microglia can have both protective and harmful roles in AD. They help clear Aβ and other debris, which may prevent the development of AD. However, when activated, microglia can mediate synapse loss, exacerbate tau pathology, and secrete inflammatory factors that damage neurons. The balance between these functions is crucial for AD progression. Genetic studies have identified several AD risk genes that are selectively expressed by microglia, including APOE, SPI1, and TREM2. These genes are involved in microglial activation, phagocytosis, and clearance of Aβ. Microglial activation states are defined by transcriptional profiling, revealing different functional states of microglia in AD. These states include a disease-associated microglial (DAM) state, which is associated with neurodegeneration. The DAM state is influenced by TREM2 and apoE, and is characterized by increased phagocytosis and clearance of Aβ. However, in some cases, microglial dysfunction can lead to neuroinflammation and neuronal damage. The dual role of microglia in AD suggests that their function is complex and context-dependent, with protective and harmful effects depending on the stage of the disease. Overall, microglia are essential for maintaining brain homeostasis and preventing AD. However, their activation can be harmful if it leads to excessive inflammation and neuronal damage. Understanding the role of microglia in AD is crucial for developing therapeutic strategies that target microglial function to prevent or treat the disease.Microglia play a critical role in Alzheimer's disease (AD) pathogenesis. They are the resident immune cells of the central nervous system (CNS) and are involved in maintaining brain homeostasis, clearing debris, and responding to pathogens. In AD, microglia become activated and aggregate around amyloid plaques, which are extracellular deposits of β-amyloid (Aβ) peptides. Human genetic studies have shown that many AD risk genes are highly expressed by microglia, suggesting their involvement in AD pathogenesis. These genes include TREM2, which is essential for microglial function and is associated with AD risk. Mutations in TREM2, such as R47H, impair microglial activation and contribute to AD progression. Microglia can have both protective and harmful roles in AD. They help clear Aβ and other debris, which may prevent the development of AD. However, when activated, microglia can mediate synapse loss, exacerbate tau pathology, and secrete inflammatory factors that damage neurons. The balance between these functions is crucial for AD progression. Genetic studies have identified several AD risk genes that are selectively expressed by microglia, including APOE, SPI1, and TREM2. These genes are involved in microglial activation, phagocytosis, and clearance of Aβ. Microglial activation states are defined by transcriptional profiling, revealing different functional states of microglia in AD. These states include a disease-associated microglial (DAM) state, which is associated with neurodegeneration. The DAM state is influenced by TREM2 and apoE, and is characterized by increased phagocytosis and clearance of Aβ. However, in some cases, microglial dysfunction can lead to neuroinflammation and neuronal damage. The dual role of microglia in AD suggests that their function is complex and context-dependent, with protective and harmful effects depending on the stage of the disease. Overall, microglia are essential for maintaining brain homeostasis and preventing AD. However, their activation can be harmful if it leads to excessive inflammation and neuronal damage. Understanding the role of microglia in AD is crucial for developing therapeutic strategies that target microglial function to prevent or treat the disease.