Tau PET overlap index correlation with neuropathological findings.

INTRODUCTION

The tau positron emission tomography (PET) overlap index (OI) has shown promise in maximizing signal-to-noise for longitudinal tau PET imaging, particularly for early tau pathology, but requires validation against neuropathology.

METHODS

Fifty-seven participants who underwent serial tau PET imaging (flortaucipir) and subsequent autopsy were included. Tau PET OI and standardized uptake value ratios (SUVRs) were compared across neuropathological diagnoses.

RESULTS

Tau PET OI showed greater concordance with neurofibrillary tangle (NFT) severity in the entorhinal cortex (a key region for Alzheimer's disease [AD] tauopathy) than SUVR, particularly in early Braak tangle stages (positivity: 52.2% for OI vs. 13.0% for SUVR). OI detected overlapping tau voxels that exhibited spatial correspondence with immunohistochemical and autoradiography measures of tau deposition across both AD and non-AD tauopathies.

DISCUSSION: These findings demonstrate the enhanced capacity of OI in serial tau PET to robustly detect early and spatially localized tau pathology, supporting its application as a sensitive imaging metric in AD and select non-AD tauopathies.