{"doi":"10.1002/alz.12610","title":"Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis","abstract":"OBJECTIVE: Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline. BACKGROUND: Amyloid-β (Aβ) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver. NEW HYPOTHESIS: AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression. MAJOR CHALLENGES: Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes. LINKAGE TO OTHER MAJOR THEORIES: Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.","journal":"Alzheimer s & Dementia","year":2022,"id":232357,"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":213,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"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":467941,"name":"Yoo Jin Jung","orcid":"0000-0002-9015-5529","position":1,"is_corresponding":false},{"id":468714,"name":"Michael T. Scerba","orcid":null,"position":2,"is_corresponding":false},{"id":715810,"name":"Inho Hwang","orcid":"0000-0003-2039-3895","position":3,"is_corresponding":false},{"id":715809,"name":"Yu Kyung Kim","orcid":"0000-0002-4699-8502","position":4,"is_corresponding":false},{"id":302064,"name":"Sun Kim","orcid":"0000-0003-3072-6649","position":5,"is_corresponding":false},{"id":843235,"name":"Sydney Modrow","orcid":null,"position":6,"is_corresponding":false},{"id":305915,"name":"David Tweedie","orcid":"0000-0002-8446-4544","position":7,"is_corresponding":false},{"id":715808,"name":"Shih‐Chang Hsueh","orcid":"0009-0002-0838-0223","position":8,"is_corresponding":false},{"id":842326,"name":"Dong Liu","orcid":"0000-0003-0451-5979","position":9,"is_corresponding":false},{"id":360809,"name":"Weiming Luo","orcid":"0009-0002-3035-3176","position":10,"is_corresponding":false},{"id":319983,"name":"Elliot J. Glotfelty","orcid":"0000-0001-5125-8720","position":11,"is_corresponding":false},{"id":319985,"name":"Yazhou Li","orcid":"0000-0002-6048-3660","position":12,"is_corresponding":false},{"id":467943,"name":"Jia‐Yi Wang","orcid":"0000-0002-9106-3351","position":13,"is_corresponding":false},{"id":546659,"name":"Yu Luo","orcid":"0000-0002-7939-5505","position":14,"is_corresponding":false},{"id":333743,"name":"Barry J. Hoffer","orcid":"0000-0002-1122-9025","position":15,"is_corresponding":false},{"id":467942,"name":"Dong Seok Kim","orcid":"0000-0001-5637-2469","position":16,"is_corresponding":false},{"id":323570,"name":"Ross A. McDevitt","orcid":"0000-0003-3722-9047","position":17,"is_corresponding":false},{"id":297917,"name":"Nigel H. Greig","orcid":"0000-0002-3032-1468","position":18,"is_corresponding":false},{"id":468713,"name":"Daniela Lecca","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:21:12.348693Z","pmid":"35234334","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":[]}