Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using 18FGSK1482160

Neuroinflammation plays an important role in Alzheimer's disease and primary tauopathies. The aim of the current study was to map 18FGSK1482160 for imaging of purinergic P2X7R in Alzheimer's disease and primary tauopathy mouse models. Small animal PET was performed using 18FGSK1482160 in widely used mouse models of Alzheimer's disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of 18FGSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau 18FAPN-1607 and 18FGSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of 18FGSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.