Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [F]GSK1482160.

Abstract

Neuroinflammation plays an important role in Alzheimer's disease and primary tauopathies. The aim of the current study was to map [F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer's disease and primary tauopathy mouse models. Small animal PET was performed using [F]GSK1482160 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 [F]GSK1482160 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 [F]APN-1607 and [F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [F]GSK1482160 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.