Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

Alzheimer's Disease (AD) is known for its profound impact on the brain, yet its systemic effects, particularly on peripheral tissues, remain underexplored. To address this gap, we utilized Drosophila, an established model for aging and neurodegeneration studies, to create the Alzheimer's Disease Fly Cell Atlas (AD-FCA). This comprehensive atlas comprises whole-organism single-nucleus transcriptomes from 219 cell types in two AD models, where adult flies express human Aβ42 or Tau exclusively in neurons. Our in-depth analyses reveal that Aβ42 prominently affects peripheral sensory neurons, whereas Tau expression leads to notable alterations in several non-neuronal tissues, including the gut, fat body, and reproductive system. The AD-FCA uncovers the nuanced interplay between neuronal pathology and peripheral tissue responses, offering novel insights into potential biomarkers and the systemic nature of AD. To know how Aβ42 and hTau impact brain neurons and periphery cells during aging, we collected 10d, 20d, and 30d flies from control, Aβ42, and hTau flies to perform snRNA-seq. Head and body were separated. Female and male were also profiled separately.