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Our review narrowly focuses on insights obtained from post\u2010mortem neuropathological examinations of human brains paying particular attention to microglia as these cells have long been implicated as pivotal players in the cellular processes that lead to AD\u2010type neurodegeneration. Although complete understanding of the roles played by microglia in AD neurodegeneration remains elusive, our studies thus far have illuminated microglial involvement in LOAD, showing that microglial dystrophy, the morphological manifestation of senescence, can be integrated with other hallmark pathological features of AD, such as intraneuronal neurofibrillary degeneration (NFD) and extracellular deposits of amyloid\u2010beta (A\u03b2) protein. We have demonstrated an in situ correlation between microglial dystrophy and presence of NFD suggesting that neurodegeneration is secondary to aging\u2010related microglial deterioration, a concept founded on the notion that proper neuronal function is dependent on presence of healthy microglia. Diseased or weakened glia are detrimental for neuronal well\u2010being because their ability to provide neuronal support may be impaired. Our most recent work also links microglial dystrophy with A\u03b2 deposits by showing that there is a chronic, yet futile microglial reaction to insoluble amyloid deposits. This inability of microglia to remove aggregated amyloid (a foreign body) causes microglial exhaustion and thereby exacerbates already ongoing aging\u2010dependent microglial deterioration. An eventual total loss of functional microglia in advanced LOAD promotes widespread NFD, dementia, and brain failure.<\/jats:p>","DOI":"10.1002\/glia.23782","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T12:52:17Z","timestamp":1578660737000},"page":"845-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":144,"title":["Dystrophic microglia in late\u2010onset Alzheimer's disease"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-9052","authenticated-orcid":false,"given":"Wolfgang J.","family":"Streit","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Florida College of Medicine  Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-8771","authenticated-orcid":false,"given":"Habibeh","family":"Khoshbouei","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Florida College of Medicine  Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Anatomical Institute University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.2008.65.7.nct70006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0209-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0789-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv236"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.12.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2233"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10389"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170711"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000202887.22082.63"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12456"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0272151"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.1223"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026317"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.10.034"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-4-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2007-11406"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2005-7304"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(87)90218-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0431"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)70016-5"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4017"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0616-08.2008"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1306.015"},{"key":"e_1_2_9_31_1","first-page":"21","article-title":"The enigma of cell death in neurodegenerative disorders","volume":"60","author":"Jellinger K. 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