High‐resolution non‐invasive whole brain imaging of tauopathy in a tauopathy mouse model

Abstract Background Abnormal tauopathy accumulation play an important role in tauopathy diseases including Alzheimer’s disease and Frontotemporal dementia. There is a gap in high‐resolution non‐invasive imaging tool for detecting tauopathy deposits in animal models. Method The binding properties of a panel of imaging probes to 4‐repeat K18 tau fibril was assessed by using Thoflavin T assay and surface plasmon resonance assay. Next we established optimal dosage for tau probes in in vivo optoacoustic imaging, and developed transcranial whole brain imaging (130 micron spatial resolution) of tauopathy in P301L model of 4‐repeat tauopathy. T2 magnetic resonance imaging at 9.4T was performed for structural information and for volume‐of‐interest analysis of optoacoustic imaging data after co‐registration. Result In vitro assay showed binding to recombinant K18 tau fibril using PBB5, THK5351, but not T‐807 or MK‐6240. i.v . administration of PBB5 in P301L mice led to a retention of PBB5 in tau ladened cortex and hippocampus by registering with structural magnetic resonance imaging data. The specificity of PBB5 was validated by immunohistochemistry with anti‐phosphorylated tau antibody AT‐100. Conclusion Optoacoustic imaging with PBB5 facilitates preclinical high‐resolution whole brain imaging of tauopathy, for studying the spreading and accumulation of tauopathy, and for monitoring putative treatments targeting tau.