Recent studies elucidate distinct molecular contributions of amyloid-β and tau proteins to Alzheimer's disease pathology in central and peripheral tissues. Single-nucleus RNA sequencing of exercise responses in Alzheimer’s mouse models reveals cell-type-specific transcriptomic restoration and identifies neurovascular astrocytes and disease-associated microglia as key mediators of exercise’s protective effects. These insights provide a comprehensive resource for understanding how physical activity modulates neurodegenerative disease progression and open avenues for novel therapeutic interventions.