Paula Beltran-Lobo, Martina M Hughes, Claire Troakes, Cara L Croft, Huzefa Rupawala, Daniel Jutzi, Marc-David Ruepp, Maria Jimenez-Sanchez, Michael S Perkinton, Michael Kassiou, Todd E Golde, Diane P Hanger, Alexei Verkhratsky, Beatriz G Perez-Nievas, Wendy Noble
The purinoceptor P2X7 R is a promising therapeutic target for tauopathies, including Alzheimer's disease (AD). Pharmacological inhibition or genetic knockdown of P2X7 R ameliorates cognitive deficits and reduces pathological tau burden in mice that model aspects of tauopathy, including mice expressing mutant human frontotemporal dementia (FTD)-causing forms of tau. However, disagreements remain over which glial cell types express P2X7 R and therefore the mechanism of action is unresolved. Here, we show that P2X7 R protein levels increase in human AD post-mortem brain, in agreement with an upregulation of P2RX7 mRNA observed in transcriptome profiles from the AMP-AD consortium...
September 15, 2023: Brain, Behavior, and Immunity