{"doi":"10.1101/2021.11.01.466525","title":"Concerted cellular responses to type I interferon propel memory impairment associated with amyloid β plaques","abstract":"Abstract Despite well-documented maladaptive neuroinflammation in Alzheimer’s disease (AD), the principal signal that drives memory and cognitive impairment remains elusive. Here, we reveal robust, age-dependent cellular reactions to type I interferon (IFN), an innate immune cytokine aberrantly elicited by β amyloid plaques, and examine their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Long-term blockade of IFN receptor rescued both memory and synaptic deficits, and also resulted in reduced microgliosis, inflammation, and neuritic pathology. Interestingly, microglia-specific IFN receptor ablation attenuated the loss of post-synaptic terminals, whereas IFN signaling in neural cells contributed to pre-synaptic alteration and plaque accumulation. Intriguingly, IFN pathway activation displayed a strong inverse correlation with cognitive performance, promoting selective synapse engulfment by microglia rather than amyloid plaques. Overall, IFN signaling represents a critical module within the neuroinflammatory network of AD and prompts a concerted cellular state that is detrimental to memory and cognition.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":227350,"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":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110455,"name":"Gabriel S. Chiu","orcid":null,"position":1,"is_corresponding":false},{"id":831249,"name":"Sanming Li","orcid":"0000-0001-8769-7135","position":2,"is_corresponding":false},{"id":110457,"name":"Nicholas E. Propson","orcid":"0000-0001-8205-3218","position":3,"is_corresponding":false},{"id":110462,"name":"Hui Zheng","orcid":"0000-0002-5427-3798","position":4,"is_corresponding":false},{"id":110463,"name":"Wei Cao","orcid":"0000-0002-8952-9159","position":5,"is_corresponding":false},{"id":110452,"name":"Ethan R. Roy","orcid":"0000-0002-0881-1620","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:54:42.179886Z","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":[]}