Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias

Abstract

IntroductionAggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [18F]AV-1451 in a range of dementias. MethodsPhosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias. Results[18F]AV-1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism-17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non–tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups. Discussion[18F]AV-1451 binds to tau in AD, and some other tauopathies. However, evidence for a non–tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic.