Language
English
Publication Date
5-23-2023
Journal
eLife
DOI
10.7554/eLife.85251
PMID
37219079
PMCID
PMC10259480
PubMedCentral® Posted Date
5-23-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Aging is a major risk factor for Alzheimer’s disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in Drosophila with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- and aging-induced gene expression strongly overlap (93%), they differ in the affected cell types. In contrast to the broad impact of aging, tau-triggered changes are strongly polarized to excitatory neurons and glia. Further, tau can either activate or suppress innate immune gene expression signatures in a cell-type-specific manner. Integration of cellular abundance and gene expression pinpoints nuclear factor kappa B signaling in neurons as a marker for cellular vulnerability. We also highlight the conservation of cell-type-specific transcriptional patterns between Drosophila and human postmortem brain tissue. Overall, our results create a resource for dissection of dynamic, age-dependent gene expression changes at cellular resolution in a genetically tractable model of tauopathy.
Keywords
Animals, Humans, tau Proteins, Neurons, Alzheimer Disease, Neuroglia, Aging, Brain, Drosophila, D. melanogaster, Human
Published Open-Access
yes
Recommended Citation
Wu, Timothy; Deger, Jennifer M; Ye, Hui; et al., "Tau Polarizes an Aging Transcriptional Signature to Excitatory Neurons and Glia" (2023). Faculty and Staff Publications. 2145.
https://digitalcommons.library.tmc.edu/baylor_docs/2145
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons