{"doi":"10.1016/j.celrep.2020.108398","title":"Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression","abstract":"To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia and bulk tissue from mouse and human AD, FTD, and PSP. We uncover a complex temporal trajectory of microglial-immune pathways involving the type 1 interferon response associated with tau pathology in the early stages, followed by later signatures of partial immune suppression and, subsequently, the type 2 interferon response. We find that genetic risk for dementias shows disease-specific patterns of pathway enrichment. We identify drivers of two gene co-expression modules conserved from mouse to human, representing competing arms of microglial-immune activation (NAct) and suppression (NSupp) in neurodegeneration. We validate our findings by using chemogenetics, experimental perturbation data, and single-cell sequencing in post-mortem brains. Our results refine the understanding of stage- and disease-specific microglial responses, implicate microglial viral defense pathways in dementia pathophysiology, and highlight therapeutic windows.","journal":"Cell Reports","year":2020,"id":54694,"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":101,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23580,"name":"Damon Polioudakis","orcid":null,"position":1,"is_corresponding":false},{"id":281535,"name":"Anna Yin","orcid":"0000-0002-1612-5532","position":2,"is_corresponding":false},{"id":27831,"name":"Vivek Swarup","orcid":"0000-0003-3762-2746","position":3,"is_corresponding":false},{"id":281536,"name":"Timothy S. Chang","orcid":"0000-0002-9225-9874","position":4,"is_corresponding":false},{"id":281537,"name":"Tam Nguyen","orcid":"0000-0002-9833-4062","position":5,"is_corresponding":false},{"id":281538,"name":"Arjun Sarkar","orcid":"0000-0001-6867-8692","position":6,"is_corresponding":false},{"id":281539,"name":"Lawrence Chen","orcid":"0000-0003-1721-2483","position":7,"is_corresponding":false},{"id":281540,"name":"Jerry I. Huang","orcid":"0000-0002-8325-1248","position":8,"is_corresponding":false},{"id":281541,"name":"Li‐Chun Lin","orcid":"0000-0001-6715-6374","position":9,"is_corresponding":false},{"id":32591,"name":"William W. Seeley","orcid":"0000-0003-1410-2027","position":10,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":11,"is_corresponding":false},{"id":2978,"name":"Dheeraj Malhotra","orcid":"0000-0003-4700-4407","position":12,"is_corresponding":false},{"id":21398,"name":"Daniel H. Geschwind","orcid":"0000-0003-2896-3450","position":13,"is_corresponding":false},{"id":281534,"name":"Jessica E. Rexach","orcid":"0000-0002-4462-7249","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-18T21:04:14.743014Z","pmid":"33207193","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":[]}