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However, the precise nature of their role in the pathogenesis of AD is debated; the major working hypothesis is that pro\u2010inflammatory activities of activated microglia contribute to disease progression. In contrast, others have proposed that microglial dystrophy with a loss of physiological and neuroprotective activities promotes neurodegeneration. This immunohistochemical study sought to gain clarity in this area by quantifying the morphological subtypes of microglia in the mildly\u2010affected primary visual cortex (PVC), the moderately affected superior frontal cortex (SFC) and the severely affected inferior temporal cortex (ITC) of 8 AD cases and 15 age and gender\u2010matched, non\u2010demented controls with ranging AD\u2010type pathology. AD cases had increased \u03b2\u2010amyloid and tau levels compared to controls in all regions. Neuronal loss was observed in the SFC and ITC, and was associated with atrophy in the latter. A major feature of the ITC in AD was a decrease in ramified (healthy) microglia with image analysis confirming reductions in arborized area and skeletal complexity. Activated microglia were not associated with AD but were increased in non\u2010demented controls with greater AD\u2010type pathology. Microglial clusters were occasionally associated with \u03b2\u2010amyloid\u2010 and tau\u2010positive plaques but represented less than 2% of the total microglial population. Dystrophic microglia were not associated with AD, but were inversely correlated with brain pH suggesting that agonal events were responsible for this morphological subtype. Overall these novel findings suggest that there is an early microglial reaction to AD\u2010type pathology but a loss of healthy microglia is the prominent feature in severely affected regions of the AD brain.<\/jats:p>","DOI":"10.1111\/bpa.12717","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T06:45:11Z","timestamp":1551163511000},"page":"726-740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["The relationship between the morphological subtypes of microglia and Alzheimer\u2019s disease neuropathology"],"prefix":"10.1111","volume":"29","author":[{"given":"Patrick Jarmo","family":"Paasila","sequence":"first","affiliation":[{"name":"Discipline of Pathology, Faculty of Medicine and Health The University of Sydney Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle 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