Multiscale Approximations to Understand the Complex Role of Microglia in Alzheimer's Disease

Microglia, the resident innate immune cells of the central nervous system, play a pivotal role in the pathogenesis of Alzheimer's disease (AD). Microglia are now recognized as a highly dynamic and heterogeneous population whose molecular and functional states vary with spatial context, disease stage, and genetic background. Recent discoveries across multiple scales from genetics, molecular and cellular biology, to systems-level imaging and epidemiology have underscored the complex and context-dependent contributions of microglia to the AD cascade. Together, these findings highlight the need for integrative, multiscale approaches that bridge molecular, cellular, and systemic perspectives to elucidate the diverse roles of microglia and their impact on disease progression. This mini-review discusses recent advances in understanding microglial biology across these dimensions and outlines current challenges toward achieving a more unified and therapeutically oriented framework for studying microglia in AD.