Towards clinical application of tau PET: Trials

Abstract

AbstractBackgroundRecent widespread availability of tau PET tracers, as well as large cross‐sectional and longitudinal datasets has now added tau PET as a well‐validated biomarker for feasible assessment and design of clinical trials. Tau PET shows potential for improved diagnosis, enrichment of populations likely to progress during a study, and for demonstration of target engagement or of a relevant downstream effect. Despite this great potential, there are still many challenges for effective implementation of tau PET in a clinical trial. Visual and quantitative methods for establishing tau positivity and even the meaningfulness of tau positivity are not well‐defined. There is no consensus on the best quantitative measures of tau progression. Further, while tau PET tracers currently used in AD drug studies show similar brain patterns of binding, enough differences exist that complicate use of multiple tau tracers for enrichment, or for comparing results from different study cohorts. Tau PET correlates more closely with clinical symptoms than amyloid PET, but further evidence needs to be generated for its acceptance as a surrogate by health authorities.ConclusionThis presentation will discuss current strategies and recent analyses in the use of tau PET for optimizing study populations in preclinical and early AD, and consideration of sample size requirements when tau PET is used as a pharmacodynamics marker. It will review use of baseline biomarkers including amyloid and tau burden to predict future tau accumulation and clinical progression. Practical considerations, including tau tracer production networks, dosimetry and participant burden will also be discussed.