{"doi":"10.1101/2022.11.14.516410","title":"Tau polarizes an aging transcriptional signature to excitatory neurons and glia","abstract":"Summary 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 as a potential marker for neuronal 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313176,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9436,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1011430,"name":"Jennifer Deger","orcid":"0000-0003-2208-3348","position":1,"is_corresponding":false},{"id":353011,"name":"Hui Ye","orcid":"0000-0003-3965-9702","position":2,"is_corresponding":false},{"id":288607,"name":"Caiwei Guo","orcid":"0000-0002-9975-9732","position":3,"is_corresponding":false},{"id":40852,"name":"Justin Dhindsa","orcid":"0000-0003-2963-0447","position":4,"is_corresponding":false},{"id":465426,"name":"Brandon Pekarek","orcid":"0000-0001-8785-4196","position":5,"is_corresponding":false},{"id":234498,"name":"Rami Al‐Ouran","orcid":null,"position":6,"is_corresponding":false},{"id":110460,"name":"Zhandong Liu","orcid":"0000-0002-7608-0831","position":7,"is_corresponding":false},{"id":585516,"name":"Ismael Al‐Ramahi","orcid":"0000-0002-1275-1114","position":8,"is_corresponding":false},{"id":585517,"name":"Juan Botas","orcid":"0000-0001-5476-5955","position":9,"is_corresponding":false},{"id":288605,"name":"Timothy Wu","orcid":"0000-0001-5296-2023","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}