2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and benzothiazoline

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. In vivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection of tau inclusions by PBBs. A pyridinated PBB, [(11)C]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, [(11)C]Pittsburgh Compound-B ([(11)C]PIB). [(11)C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [(11)C]PBB3 signals were found in a corticobasal syndrome patient negative for [(11)C]PIB-PET.

Topics: Age Factors; Aged; Alzheimer Disease; Aminopyridines; Amyloid beta-Peptides; Aniline Compounds; Animals; Autoradiography; Benzothiazoles; Brain; Brain Mapping; Calcium-Binding Proteins; Carbon Isotopes; Disease Models, Animal; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Humans; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins; Middle Aged; Mutation; Positron-Emission Tomography; Protein Structure, Secondary; tau Proteins; Tauopathies; Thiazoles