P2Y12 receptor is expressed on human microglia under physiological conditions throughout development and is sensitive to neuroinflammatory diseases.

Microglia are resident immune cells in the central nervous system (CNS), which are essential for immune defence and critically contribute to neuronal functions during homeostasis. Until now, little is known about microglia biology in humans in part due to the lack of microglia-specific markers. We therefore investigated the expression of the purinergic receptor P2Y12 in human brain tissue. Compared to classical markers used to identify microglia such as Iba1, CD68 or MHCII, we found that P2Y12 is expressed on parenchymal microglia but is absent from perivascular or meningeal macrophages. We further demonstrate that P2Y12 expression is stable throughout human brain development, including fetal phases, and quantification of P2 Y12+ microglia revealed that the density of human microglia is constant throughout lifetime. In contrast, CD68 expression increases during aging in cerebellar but not in cortical microglia, indicating regional heterogeneity. CNS pathologies such as Alzheimer's disease or multiple sclerosis-but not schizophrenia-result in decreased P2Y12 immunoreactivity in plaque- or lesion-associated myeloid cells, whereas Iba1 expression remains detectable. Our results suggest that P2Y12 is a useful marker for the identification of human microglia throughout the lifespan. Moreover, P2Y12 expression might help to discriminate activated microglia and infiltrating myeloid cells from quiescent microglia in the human CNS. GLIA 2017;65:375-387.