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• W2896288324 abstract "Activated microglia are a feature of Alzheimer's disease (AD) pathology, and inflammatory mechanisms are considered to contribute to AD neurodegeneration. Purinergic receptor P2RY12, a microglial specific receptor for ADP/ATP, is a unique marker as it is hypothesized to identify only non-activated microglia. In vitro studies with human microglia have shown that P2RY12 is upregulated by interleukin-4 identifying its expression as an alternative activation marker. Immunohistochemistry for this marker in brain sections may define the distribution of activated and non-activated microglia associated with AD pathology. This study employed fixed human brain tissue sections of middle temporal gyrus (MTG) from a series of low plaque (LP)(n=12), high plaque (HP)(n=14) non-demented (ND), and AD (n=14) cases. Cellular localization of P2RY12 was identified by light and confocal immunohistochemistry with colocalization of P2RY12 immunoreactivity identified with antibodies to amyloid beta (Aβ), phosphorylated tau (pTAU), and microglial markers IBA-1, HLA-DR, CD68 and progranulin. P2RY12 immunohistochemistry identified microglia with a range of morphologies. LP cases mostly had P2RY12 microglia with ramified/resting morphologies, but with increasing plaque and tangle pathology, there were fewer positive microglia but many of these were more strongly P2RY12 positive with activated morphologies. There was no significant difference between disease groups using quantitative measures indicating that factors affecting P2RY12 expression were not widespread. The type of Aβ plaque (neuritic, diffuse, cored) appeared to affect the surrounding P2RY12-positive microglia. Confocal microscopy showed P2RY12 and HLA-DR, a marker of activated microglia, could be colocalized in some microglia, but most HLA-DR-positive microglia were negative for P2RY12. Many P2RY12 microglia in AD cases were positive for the phagocytic marker CD68. In areas surrounding Aβ plaques, P2RY12-microglia were mostly absent. HLA-DR-positive microglia clustered on plaques were usually P2RY12 negative. By contrast, most AT8-positive structures, except for neuritic plaques, did not appear to influence P2RY12 expression. The findings from this study show that P2RY12 immunoreactivity identifies non-activated microglia, as expected, but also appears to identify some types of activated microglia. The lack of P2RY12-positive microglia around many plaques may represent localized zones of inflammation induced by the activated microglia clustered on the Aβ plaques." @default.
• W2896288324 created "2018-10-26" @default.
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• W2896288324 date "2018-07-01" @default.
• W2896288324 modified "2023-10-16" @default.
• W2896288324 title "P4‐191: FEATURES OF PURINERGIC RECEPTOR P2RY12 IMMUNOREACTIVE MICROGLIA IN ALZHEIMER'S DISEASE AND NON‐DEMENTED AGED BRAINS: ARE P2RY12 POSITIVE MICROGLIA NON‐ACTIVATED?" @default.
• W2896288324 doi "https://doi.org/10.1016/j.jalz.2018.06.2596" @default.
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