Language
English
Publication Date
7-9-2025
Journal
Neuron
DOI
10.1016/j.neuron.2025.04.017
PMID
40381615
PMCID
PMC12245608
PubMedCentral® Posted Date
5-16-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
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 AD Fly Cell Atlas (AD-FCA) based on whole-organism single-nucleus transcriptomes of 219 cell types from flies expressing AD-associated proteins, either human amyloid-β 42 peptide (Aβ42) or Tau, in neurons. We found that Aβ42 primarily affects the nervous system, including sensory neurons, while Tau induces accelerated aging in peripheral tissues. We identified a neuronal cluster enriched in Aβ42 flies, which has high lactate dehydrogenase (LDH) expression. This LDH-high cluster is conserved in 5XFAD mouse and human AD datasets. We found a conserved defect in fat metabolism 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 communication in neurodegeneration.
Keywords
Animals, Amyloid beta-Peptides, tau Proteins, Mice, Humans, Peptide Fragments, Alzheimer Disease, Drosophila, Neurons, Mice, Transgenic, Disease Models, Animal, Tauopathies, Transcriptome, Alzheimer’s disease, neurodegeneration, aging, Drosophila, single-nucleus RNA-seq, cell atlas
Published Open-Access
yes
Recommended Citation
Park, Ye-Jin; Lu, Tzu-Chiao; Jackson, Tyler; et al., "Distinct Systemic Impacts of Aβ42 and Tau Revealed by Whole-Organism snRNA-Seq" (2025). Faculty, Staff and Students Publications. 7047.
https://digitalcommons.library.tmc.edu/baylor_docs/7047
Graphical Abstract