Increased regional P2X7R expression detected by GSK1482160 PET in a tauopathy mouse model

Kong, Y.; Cao, L.; Wang, J.; Zhuang, J.; Liu, Y.; Bi, L.; Qiu, Y.; Hou, Y.; Huang, Q.; Xie, F.; Yang, Y.; Shi, K.; Rominger, A.; Guan, Y.; Jin, H.; Ni, R.

doi:10.1101/2024.01.27.575823

bioRxiv · 10.1101/2024.01.27.575823

Increased regional P2X7R expression detected by GSK1482160 PET in a tauopathy mouse model

Kong, Y.·Cao, L.·Wang, J.·Zhuang, J.·Liu, Y.·Bi, L.·Qiu, Y.·Hou, Y.·Huang, Q.·Xie, F.·Yang, Y.·Shi, K.·Rominger, A.·Guan, Y.·Jin, H.·Ni, R.

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Abstract

Neuroinflammation plays an important role in Alzheimers disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimers disease and primary tauopathy mouse models. MicroPET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimers disease (APP/PS1, 5xFAD and 3xTg), 4-repeat tauopathy (rTg4510) mice and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the cortex and basal forebrain of 7-month-old rTg4510 mice compared to age-matched wild-type mice and compared to 3-month-old rTg4510 mice. Nonparametric Spearmans rank analysis revealed a positive correlation between tau [18F]APN-1607 uptake and [18F]GSK1482160 in the hippocampus of rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 were observed between wild-type mice and APP/PS1 mice (5, 10 months), 5xFAD mice (3, 7 months) or 3xTg mice (10 months). Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion compared to wild-type mice. These findings provide in vivo imaging evidence for increased P2X7R in the brains of tauopathy model mice.

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Kong, Y., Cao, L., Wang, J., Zhuang, J., Liu, Y., Bi, L., Qiu, Y., Hou, Y., Huang, Q., Xie, F., Yang, Y., Shi, K., Rominger, A., Guan, Y., Jin, H., Ni, R.. 2024-01-28. Increased regional P2X7R expression detected by GSK1482160 PET in a tauopathy mouse model. https://doi.org/10.1101/2024.01.27.575823

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