Brain pathology
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Microglial associations with both the major Alzheimer's disease (AD) pathognomonic entities, β-amyloid-positive plaques and tau-positive neurofibrillary tangles, have been noted in previous investigations of both human tissue and mouse models. However, the precise nature of their role in the pathogenesis of AD is debated; the major working hypothesis is that pro-inflammatory 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. ⋯ Microglial clusters were occasionally associated with β-amyloid- and tau-positive 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-type pathology but a loss of healthy microglia is the prominent feature in severely affected regions of the AD brain.