Exploring social modulation: Microglia as a key mediator of individual immune response, plasticity and pathology in App-NL-G-F mouse model of Alzheimer's disease

This study explores the influence of lifestyle on Alzheimer's disease (AD) progression using App-NL-G-F mice in a complex enrichment system. Mice exhibited social deficits before plaque pathology or memory impairment, revealing a crucial link between lifestyle, behavior, and neuroinflammation. Plasma analysis indicates early inflammation and apoptosis-related changes, setting the stage for identifying markers predicting plaque manifestation. Beyond pathology, social behavior is linked to adult neurogenesis and microglia coverage, forming a dynamic connection with microglia activation. Further, sc-RNA sequencing unveiled a decrease in interferon-responsive microglia and alteration in antigen processing with enrichment. These findings underscore the beneficial impact of social housing on microglia and interconnected factors, pointing to microglia as a critical mediator of the behavior-pathology- plasticity interplay in AD. The study enhances our understanding of AD complexity and offers insights into potential therapeutic strategies, emphasizing the multifaceted nature of AD progression and the role of lifestyle in shaping its course. ### Competing Interest Statement The authors have declared no competing interest.