P2X7 Receptor and Neuroinflammation in Neurodegenerative Disorders: An Autoradiography Study with [18F]JNJ-64413739

Abstract Background Neuroinflammation plays a crucial role in neurodegenerative disorders such as Alzheimer’s disease (AD). The P2X7 receptor (P2X7R), expressed on microglia, is involved in neuroinflammatory responses. Despite evidence of P2X7R upregulation in AD models, its role in human AD remains unclear. The PET radioligand [18F]JNJ-64413739 enables the assessment of P2X7R distribution in post-mortem AD brain tissue. Methods Post-mortem brain tissue from AD and control subjects was obtained. [18F]JNJ-64413739 was synthesised and applied to tissue sections from the temporal and parietal cortex. Autoradiography was conducted with and without the P2X7R antagonist JNJ54173717. Results [18F]JNJ-64413739 binding was observed across all brain regions, with effective blocking confirming specificity. No significant differences were found between AD and controls in the temporal (p = 0.84) or parietal cortex (p = 0.90) in the first experiment. Second experiment, using a modified protocol, also did not reveal a significant difference between controls and AD in either the temporal (p= 0.66) or parietal cortex (p=0.38). White matter exhibited significantly higher binding than grey matter (p < 0.01), but no disease-specific differences were noted. Conclusion This study demonstrates P2X7 receptor-specific binding of [18F]JNJ-64413739 but finds no significant differences between postmortem tissue of AD cases and controls. These findings suggest that while the tracer shows promising in vitro characteristics, the role of P2X7R in AD pathology and its utility as a biomarker require further validation through in vivo imaging studies across disease stage.