Comparative neuropathological evaluation of pT217 immunoreactivity in human and transgenic mouse tauopathies.

Abstract

Tau phosphorylation at threonine 217 (pT217) has been increasingly recognized as a biomarker for Alzheimer disease (AD), but its neuropathological distribution and the performance of available antibodies remain to be fully characterized. In this study, we performed a comparative evaluation of a recombinant rabbit monoclonal anti-pT217 antibody (mAb) using immunohistochemical and biochemical analyzes in human and transgenic mouse tauopathies and compared results to those of a commercially available anti-pT217 antibody and the AT8 antibody. In rTg4510 mice, the anti-pT217 mAb detected pathological tau aggregates with high sensitivity, including hyperphosphorylated tau species identified by biochemical fraction. In human postmortem brain tissues (AD, Pick disease, progressive supranuclear palsy, corticobasal degeneration), quantitative image analysis demonstrated labeling of a broad range of tau lesions, including neurofibrillary tangles, neuropil threads, tufted astrocytes, astrocytic plaques, and Pick bodies. The overall detectability was comparable to that of AT8 and similar to or modestly > that of a representative commercial anti-pT217 antibody. These findings indicate that pT217 is widely present across tauopathies and suggest that the recombinant anti-pT217 mAb provides a sensitive and reproducible tool for neuropathological assessment. Together, these results provide a framework for evaluating anti-pT217 antibodies in neuropathological studies.