Imaging of tau pathology in a tauopathy mouse model and in alzheimer patients compared to normal controls

Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer@s disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. Invivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection oftau inclusions by PBBs. A pyridinated PBB, [¹¹C]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [¹¹C]Pittsburgh Compound-B ([¹¹C]PIB). [¹¹C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [¹¹C]PBB3 signals were found in a corticobasal syndrome patient negative for [¹¹C]PIB-PET