{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:34:37Z","timestamp":1793838877504,"version":"4.6.1"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM124977"],"award-info":[{"award-number":["R35 GM124977"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG028383"],"award-info":[{"award-number":["P30 AG028383"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21AG066865"],"award-info":[{"award-number":["R21AG066865"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurobiology of Aging"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.neurobiolaging.2020.12.003","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T22:56:16Z","timestamp":1610060176000},"page":"19-27","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":173,"special_numbering":"C","title":["Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain"],"prefix":"10.1016","volume":"99","author":[{"given":"Ryan K.","family":"Shahidehpour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Higdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole G.","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-0411","authenticated-orcid":false,"given":"Janna H.","family":"Neltner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eseosa T.","family":"Ighodaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ela","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-0643","authenticated-orcid":false,"given":"Douglas","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Bachstetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40478-015-0209-z","article-title":"Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging","volume":"3","author":"Bachstetter","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib2","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-beta dependent molecular and functional signature in microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib4","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/bpa.12456","article-title":"Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease","volume":"27","author":"Davies","year":"2017","journal-title":"Brain Pathol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib5","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1002\/cne.24484","article-title":"Microglia changes associated to Alzheimer's disease pathology in aged chimpanzees","volume":"526","author":"Edler","year":"2018","journal-title":"J.\u00a0Comp. Neurol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jnen\/nlx097","article-title":"Detergent insoluble proteins and inclusion body-like structures immunoreactive for PRKDC\/DNA-PK\/DNA-PKcs, FTL, NNT, and AIFM1 in the amygdala of cognitively impaired elderly persons","volume":"77","author":"Gal","year":"2018","journal-title":"J.\u00a0Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib7","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/nn.4597","article-title":"Transcriptomic analysis of purified human cortical microglia reveals age-associated changes","volume":"20","author":"Galatro","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib8","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular senescence: defining a path forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1699-0463.1988.tb05320.x","article-title":"Some new, simple and efficient stereological methods and their use in pathological research and diagnosis","volume":"96","author":"Gundersen","year":"1988","journal-title":"APMIS"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib10","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/ana.23974","article-title":"Iron and neurodegeneration in the multiple sclerosis brain","volume":"74","author":"Hametner","year":"2013","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/ncb2811","article-title":"Transmitting senescence to the cell neighbourhood","volume":"15","author":"Hoare","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/1742-2094-8-171","article-title":"Neuroinflammation in Alzheimer's disease wanes with age","volume":"8","author":"Hoozemans","year":"2011","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/mp.2017.246","article-title":"Markers of microglia in post-mortem brain samples from patients with Alzheimer's disease: a systematic review","volume":"23","author":"Hopperton","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib14","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","article-title":"Geroscience: linking aging to chronic disease","volume":"159","author":"Kennedy","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib15","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A\u00a0unique microglia type Associated with restricting development of Alzheimer's disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib16","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/glia.20678","article-title":"Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity","volume":"56","author":"Lopes","year":"2008","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib17","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Lopez-Otin","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer's disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fchem.2019.00136","article-title":"Iron redox speciation analysis using capillary electrophoresis coupled to inductively coupled plasma mass spectrometry (CE-ICP-MS)","volume":"7","author":"Michalke","year":"2019","journal-title":"Front. Chem."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib20","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1002\/glia.23477","article-title":"A\u00a0limited capacity for microglial repopulation in the adult brain","volume":"66","author":"Najafi","year":"2018","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2013.07.008","article-title":"Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice","volume":"35","author":"Orre","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib22","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neurobiolaging.2019.02.010","article-title":"Old age increases microglial senescence, exacerbates secondary neuroinflammation, and worsens neurological outcomes after acute traumatic brain injury in mice","volume":"77","author":"Ritzel","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib23","doi-asserted-by":"crossref","first-page":"e22956","DOI":"10.1002\/ajp.22956","article-title":"Loss of ferritin-positive microglia relates to increased iron, RNA oxidation, and dystrophic microglia in the brains of aged male marmosets","volume":"81","author":"Rodriguez-Callejas","year":"2019","journal-title":"Am. J. Primatol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib24","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1002\/glia.23804","article-title":"Increased oxidative stress, hyperphosphorylation of tau, and dystrophic microglia in the hippocampus of aged Tupaia belangeri","volume":"68","author":"Rodriguez-Callejas","year":"2020","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib25","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00401-016-1630-5","article-title":"Soluble phospho-tau from Alzheimer's disease hippocampus drives microglial degeneration","volume":"132","author":"Sanchez-Mejias","year":"2016","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib26","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/glia.20526","article-title":"Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease","volume":"55","author":"Simmons","year":"2007","journal-title":"Glia"},{"issue":"Pt 2","key":"10.1016\/j.neurobiolaging.2020.12.003_bib27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-2818.1984.tb02501.x","article-title":"The unbiased estimation of number and sizes of arbitrary particles using the disector","volume":"134","author":"Sterio","year":"1984","journal-title":"J.\u00a0Microsc."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib28","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00401-009-0556-6","article-title":"Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease","volume":"118","author":"Streit","year":"2009","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib29","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/glia.23782","article-title":"Dystrophic microglia in late-onset Alzheimer's disease","volume":"68","author":"Streit","year":"2020","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib30","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/glia.10319","article-title":"Dystrophic microglia in the aging human brain","volume":"45","author":"Streit","year":"2004","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbi.2015.10.012","article-title":"Microglia in dementia with Lewy bodies","volume":"55","author":"Streit","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib32","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1002\/glia.23024","article-title":"Inhomogeneous distribution of Iba-1 characterizes microglial pathology in Alzheimer's disease","volume":"64","author":"Tischer","year":"2016","journal-title":"Glia"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.neurobiolaging.2020.01.003","article-title":"Microglial activation arises after aggregation of phosphorylated-tau in a neuron-specific P301S tauopathy mouse model","volume":"89","author":"van Olst","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.neuro.2010.11.003","article-title":"Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates","volume":"32","author":"Verina","year":"2011","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.neurobiolaging.2020.12.003_bib35","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00401-011-0864-5","article-title":"Microglial pathology in Down syndrome","volume":"122","author":"Xue","year":"2011","journal-title":"Acta Neuropathol."}],"container-title":["Neurobiology of Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197458020304127?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197458020304127?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:35:00Z","timestamp":1759318500000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0197458020304127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":35,"alternative-id":["S0197458020304127"],"URL":"https:\/\/doi.org\/10.1016\/j.neurobiolaging.2020.12.003","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.30.228999","asserted-by":"object"}]},"ISSN":["0197-4580"],"issn-type":[{"value":"0197-4580","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain","name":"articletitle","label":"Article Title"},{"value":"Neurobiology of Aging","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neurobiolaging.2020.12.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}