Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States
Jennifer M Deger
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Department of Neuroscience, Baylor College of Medicine, Houston, United States
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Department of Neurology, Baylor College of Medicine, Houston, United States
Caiwei Guo
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Department of Neuroscience, Baylor College of Medicine, Houston, United States
Justin Dhindsa
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States
Brandon T Pekarek
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States
Rami Al-Ouran
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States
Zhandong Liu
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Department of Pediatrics, Baylor College of Medicine, Houston, United States; Center for Alzheimer’s and Neurodegenerative Diseases, Baylor College of Medicine, Houston, United States
Ismael Al-Ramahi
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Center for Alzheimer’s and Neurodegenerative Diseases, Baylor College of Medicine, Houston, United States
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Center for Alzheimer’s and Neurodegenerative Diseases, Baylor College of Medicine, Houston, United States
Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Department of Neuroscience, Baylor College of Medicine, Houston, United States; Department of Neurology, Baylor College of Medicine, Houston, United States; Center for Alzheimer’s and Neurodegenerative Diseases, Baylor College of Medicine, Houston, United States
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.
