Both neuronal and peripheral tissues become disrupted in Alzheimer's disease (AD). However, a comprehensive understanding of how AD impacts different tissues across the whole organism is lacking. Using Drosophila, we generated an Alzheimer's Disease Fly Cell Atlas (AD-FCA) based on whole-organism single-nucleus transcriptomes of 219 cell types from flies expressing AD-associated proteins, either human Aβ42 or Tau, in neurons. We found that neuronal Aβ42 primarily affects the nervous system, including sensory neurons, while neuronal Tau induces accelerated aging in peripheral tissues, including the fat body, gut, and reproductive system. We identified a cluster of neurons enriched in Aβ42 flies, which has high lactate dehydrogenase (LDH) expression. This LDH-high cluster is conserved in the 5XFAD mouse and human AD datasets. In contrast, we found a conserved defect in fat metabolism in adipose tissue from both fly and mouse tauopathy models. The AD-FCA offers new insights into how Aβ42 or Tau systemically and differentially affects a whole organism and provides a valuable resource for understanding brain-body communications in neurodegeneration.
- (03.13.2024) Release of AD-FCA v1.0
Park, Y.-J., Lu, T.-C., Jackson, T., Goodman, L.D., Ran, L., Chen, J., Liang, C.-Y., Harrison, E., Ko, C., Hsu, A.-L., et al. (2024). Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models. 2024.03.10.584317. https://doi.org/10.1101/2024.03.10.584317.
https://hongjielilab.shinyapps.io/ADFCA/
Cell-type annotation column: adfca_annotation
[GEO#: GSE261656]