Alzheimer's Imaging Consortium.

Area of Science:

• Neuroimaging
• Nuclear Medicine
• Alzheimer's Disease Research

Background:

• Tau PET imaging is crucial for Alzheimer's disease (AD) diagnosis, but dichotomized thresholds present analytical challenges.
• Understanding the continuous nature of tau PET measures and the 'gray zone' is vital for accurate interpretation.
• This study addresses the need for standardized tau PET thresholds across different tracers.

Purpose of the Study:

• To determine confidence levels of tau PET abnormality thresholds for various tracers.
• To characterize the 'gray zone' of tau PET positivity using the universal tau PET scale (Uniτ).
• To compare tau PET threshold consistency between MK6240 and Flortaucipir tracers.

Main Methods:

• Evaluated 485 individuals across the aging and AD spectrum using head-to-head MK6240 and Flortaucipir PET scans.
• Derived Uniτ estimates from the Meta-Temporal ROI and defined tau positivity (T+) based on standardized values.
• Utilized logistic regression and physician visual assessment (TVR+) to define a 'gray zone' for tau positivity.

Main Results:

• The Uniτ gray zone showed high consistency between MK6240 and Flortaucipir tracers, with minimal decimal differences.
• Liberal T+ thresholds (11.0) closely matched the 50% TVR+ probability threshold for both tracers.
• Higher TVR+ probabilities corresponded to near-identical increased Uniτ values for both tracers, with 26 and 47 participants falling in the gray zone for MK6240 and Flortaucipir, respectively.

Conclusions:

• Uniτ offers a standardized method for assessing tau positivity across different PET tracers.
• Combining quantitative Uniτ measures with visual assessment improves understanding of tau positivity certainty.
• This approach enhances diagnostic confidence, especially in the transition between tau-negative and tau-positive classifications.