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

Ye-Jin Park; Tzu‐Chiao Lu; Tyler Jackson; Lindsey D. Goodman; L. Ran; Jiaye Chen; Chung‐Yi Liang; Erin M Harrison; Christina Ko; Xi Xian Chen; Baiping Wang; Ao‐Lin Hsu; Elizabeth Ochoa; Kevin F. Bieniek; Shinya Yamamoto; Yi Zhu; Hui Zheng; Yanyan Qi; Hugo Jozef Bellen; Hongjie Li

doi:10.1016/j.neuron.2025.04.017

GeneticsNeuronJul 1, 2025

Peer-reviewed journal article

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

Ye-Jin Park iD, Tzu‐Chiao Lu iD, Tyler Jackson iD, Lindsey D. Goodman iD, L. Ran iD, Jiaye Chen iD, Chung‐Yi Liang iD, Erin M Harrison iD, Christina Ko iD, Xi Xian Chen iD, Baiping Wang iD, Ao‐Lin Hsu iD, Elizabeth Ochoa iD, Kevin F. Bieniek iD, Shinya Yamamoto iD, Yi Zhu iD, Hui Zheng iD, Yanyan Qi iD, Hugo Jozef Bellen iD, Hongjie Li iD

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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