{"doi":"10.1016/j.neurobiolaging.2020.12.003","title":"Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain","abstract":"Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.","journal":"Neurobiology of Aging","year":2021,"id":147095,"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":175,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":563932,"name":"Rebecca E. Higdon","orcid":null,"position":1,"is_corresponding":false},{"id":563933,"name":"Nicole G. Crawford","orcid":null,"position":2,"is_corresponding":false},{"id":563086,"name":"Janna H. Neltner","orcid":"0000-0002-2843-0411","position":3,"is_corresponding":false},{"id":245005,"name":"Eseosa T. Ighodaro","orcid":"0000-0003-1186-1394","position":4,"is_corresponding":false},{"id":563934,"name":"Ela Patel","orcid":null,"position":5,"is_corresponding":false},{"id":563087,"name":"D. A. Price","orcid":"0000-0003-3453-0643","position":6,"is_corresponding":false},{"id":245009,"name":"Peter T. Nelson","orcid":"0000-0002-6161-1265","position":7,"is_corresponding":false},{"id":318259,"name":"Adam D. Bachstetter","orcid":"0000-0003-4646-6757","position":8,"is_corresponding":false},{"id":563085,"name":"Ryan K. Shahidehpour","orcid":"0000-0003-0170-9014","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:42:30.206628Z","pmid":"33422891","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":[]}