Microglia-Mediated Phagocytosis in Alzheimer’s Disease: Mechanisms, Heterogeneity, and Therapeutic Insights

Abstract

Microglia are the resident immune cells of the CNS, maintaining brain homeostasis partially through phagocytosis. In Alzheimer's disease (AD), microglial phagocytosis is significantly impaired, contributing to the accumulation of pathological aggregates. Microglial phenotypes are dynamic and can shift depending on the disease stage and local environment. While some subpopulations retain or enhance phagocytic activity, especially under inflammatory conditions, others lose their capacity to clear toxic debris effectively. This variability underscores the need for a more nuanced understanding of microglial regulation and function. This paper explores the dual role of microglial phagocytosis in AD and discusses the emerging insights into microglial heterogeneity and how phenotypic shifts affect phagocytic capacity throughout disease progression. A comprehensive understanding of microglial phagocytosis and its dysregulation in AD is essential for designing targeted treatments. Modulating microglial activity to enhance their protective roles without triggering harmful inflammation represents a promising direction for therapeutic intervention in AD.