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

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.; Yamamoto, S.; Qi, Y.; Bellen, H. J.; Li, H.

doi:10.1101/2024.03.10.584317

bioRxiv · 10.1101/2024.03.10.584317

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

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.·Yamamoto, S.·Qi, Y.·Bellen, H. J.·Li, H.

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Abstract

Peripheral tissues become disrupted in Alzheimers Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, A{beta}42 and Tau, in neurons impacts the periphery is lacking. Using Drosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimers Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human A{beta}42 or Tau. In-depth analyses and functional data reveal impacts on peripheral sensory neurons by A{beta}42 and on various non-neuronal peripheral tissues by Tau, including the gut, fat body, and reproductive system. This novel AD atlas provides valuable insights into potential biomarkers and the intricate interplay between the nervous system and peripheral tissues in response to AD-associated proteins.

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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., Yamamoto, S., Qi, Y., Bellen, H. J., Li, H.. 2024-03-13. Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models. https://doi.org/10.1101/2024.03.10.584317

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