Development and validation of global tau severity score in Alzheimer's disease using Florzolotau (18F) PET

Tau-specific positron emission tomography (tau-PET) is valuable for assessing Alzheimer's disease (AD) severity, with phenotypic differences between young-onset AD (YOAD) and late-onset AD (LOAD) likely driven by distinct relationships between tau pathology and cognition.

This study developed a global tau severity (gTS) scale using Florzolotau (18F) PET and compared it with the CenTauR score for standardizing tau burden quantification.

A total of 186 participants were enrolled, including a pilot group (15 cognitive unimpaired controls [CTL], 15 AD patients) and a validation group (27 CTL, 67 YOAD, and 62 LOAD patients). In the validation group, cutoffs for diagnosing YOAD and LOAD using the gTS or CenTauR score were calculated.

The white matter region was identified as the most suitable reference for Florzolotau (18F). The gTS cutoff values of 24.1 for both AD and YOAD and 34.1 for LOAD demonstrated the highest diagnostic accuracy, as indicated by the area under the curve (AUC). The gTS score showed a higher AUC compared to CenTauR in YOAD versus CTL or LOAD versus CTL. The gTS scores significantly predicted total scores and subdomains on cognitive ability screening instruments. Cognitive-gTS curve features were found to have quadratic and linear relationships with YOAD and LOAD, respectively, illustrating different relationships between gTS scores and cognition.

The gTS score, derived from Florzolotau (18F) PET scans, provides significant predictions regarding tau burden and cognitive measurements. The higher AUC of gTS compared to the CenTauR universal scores indicates that gTS scores offer a robust method for differentiating AD from CTL.