Microglia-Associated Neuroinflammation in Alzheimer’s Disease and Its Therapeutic Potential

Background: Neuroinflammation has long been implicated in the progression of amyloid beta (Aβ) accumulation and the decline of cognitive function in Alzheimer’s disease (AD). The phenotype balance between A1 (toxic) and A2 (safe) microglial phenotypes to toxic illness in AD has become a hot research topic at present. Currently, many transcription factors, downstream signaling pathways, and molecular mechanisms that regulate the polarization of microglia are being explored. Furthermore, microglia may also exert a complex role in AD through the transformation of Aβ plaques or debris clearance, reflected in Aβ phagocytosis. One of the mediators of neuroinflammation in AD is the activated microglia. Therefore, the regulation of microglial function may be the key to successfully treating AD. Methods: This paper is a review article. PubMed, Embase, Scopus, and research meeting abstracts were searched up to 2024 for studies of microglia and neuroinflammation in Alzheimer’s Disease. Systematic information retrieval was performed, and appropriate studies were isolated based on important information available in the studies. The information from each of the articles was understood and extracted to form a database. Results: The similar neuropathological results between several animals and AD cases show the possibility of implementing microglia-related changes as an earlier diagnostic marker for AD in humans. The gene sets identified in various transcriptomic studies further foster this avenue of research by offering potential targets for therapeutic development. Substantial evidence, both in vitro and in vivo, has suggested that the loss of the normal A2 phenotype and the activation of toxic A1 microglia contribute to neurodegeneration in AD. Conclusions: Promoting or restoring the polarization of microglia towards the A2 phenotype may thus represent an effective therapeutic strategy for ameliorating neuroinflammation and progressive neurocognitive impairments. Multiple studies suggest that microglia-associated neuroinflammation at a special stage could also be protective, and, therefore, intervention should be delicate so that a beneficial response is retained.