Microglia networks within the tapestry of alzheimer’s disease through spatial transcriptomics

Abstract

Understanding Alzheimer’s disease (AD) at the cellular level requires insights into how diverse cell types respond to hallmark pathologies, including amyloid plaques and tau aggregates. Although single-cell transcriptomic approaches have illuminated the trajectories of AD progression in both animal models and human brains, they often lack the spatial context necessary to fully comprehend cell–cell interactions and microenvironmental influences. In this review, we discuss recent advances in spatial transcriptomics—integrating both imaging- and sequencing-based methods—that map gene expression within intact brain tissues. We highlight how these technologies have revealed regional heterogeneity and functional diversity among microglia, and their dynamic interactions with astrocytes, neurons, and oligodendrocytes in both aging and AD. Emphasis is placed on the interactions of microglia within the amyloid plaque niche, their contribution to synaptic degeneration, and how aging accelerates microglial and glial activation. By synthesizing findings from AD mouse models and physiologically characterized human tissues, we provide a comprehensive view of the cellular interplay driving AD pathogenesis and offer insights into potential therapeutic avenues.