Effect of a Novel Adenosine A2a Receptor Antagonist MB204 on Tau Hyperhosphorylation In Vivo

Multiple Tau epitopes were studied. In the cortex: reductions were seen in the phosphorylation at AT270, AT8 were seen in both MB204 and Li treatment (both p<0.001). A reduction was only seen with MB204 for pT205 (p<0.001) and only seen with lithium for the pS409 epitope (p<0.001). In the hippocampus: reductions were seen in the phosphorylation at pS40K were seen in both MB204 and Li treatment (both p<0.05 and 0.001 respectively). A reduction was only seen with MB204 for the AT8 epitope (p<0.05) and only seen for lithium for the AT270 and pT205 epitope (p<0.01 and 0.001) CONCLUSION: Acute oral treatment of mice with MB204 reduced anesthesia induced Tau hyperphosphorylation at key clinically relevant Tau epitopes. These findings highlight MB204 potential as a therapeutic agent for AD and related tauopathies.