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IntroductionTau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.MethodsUsing head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale.ResultsA strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach.DiscussionPreliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification.HighlightsTested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Background: Tau positron emission tomography (PET) is increasingly used in the clinical evaluation of patients and as an outcome measure in Alzheimer's disease (AD) clinical trials. Due to differences in tracer properties, instrumentation, and methods of analysis, however, tau‐PET outcome data cannot currently be meaningfully compared or combined. Here, we tested i) the feasibility of adapting the Centiloid method—an approach originally developed to standardize amyloid PET—to harmonize tau‐PET quantification (CenTauRs); ii) the performance of a non‐linear mixed model‐based approach (Joint Propagation Model) that does not require the use of a reference tracer. Methods: Head‐to‐head tau‐PET data (Table 1) was included from two cohorts ([18F]RO948 vs [18F]flortaucipir, n = 37 [BioFINDER‐2]; [18F]flortaucipir [Avid A05] vs [18F]MK‐6240, n = 15, University of Pittsburgh) in which each participant was scanned with two tau‐PET tracers. Standardized uptake value ratio (SUVR) values were calculated using the inferior cerebellar cortex as the reference region. Anchor point data (Table 1) was derived for each tracer using the following criteria: CenTauR‐0, cognitively unimpaired (CU), amyloid PET negative (<10 Centiloids); CenTauR‐100, amyloid PET positive (>50 Centiloids), typical (temporoparietal) AD pattern on tau‐PET visual read, age<65 andMMSE>20. Regions‐of‐interest (ROIs) included a universal tau‐PET ROI—based on the intersection of tracer specific ([18F]flortaucipir, [18F]MK‐6240, [18F]PI‐2620, [18F]PM‐PBB3, [18F]GTP1 and [18F]RO948) masks that had been derived by subtracting average of amyloid‐negative CU images from the average AD image—as well as four subregions delineated within this ROI (medial temporal, meta‐temporal, temporoparietal and frontal) (Figure 1A). An overview of the adapted Centiloid‐like approach and the joint propagation model is shown in Figure 1B. Results: High R2 values were observed between tracers across all ROIs: [18F]RO948 vs [18F]flortaucipir, average 0.965 [range 0.923 (frontal) to 0.986 (universal)]; [18F]MK‐6240 vs [18F]flortaucipir, average 0.985 [range, 0.923 (medial temporal) to 0.991 (frontal)]. The Centiloid‐like and joint propagation model approaches provided near identical CenTauR values (Figure 2). Conclusions: Preliminary findings support the development of standardized scale for tau‐PET using both a Centiloid‐like or joint propagation model approach. Additional data and consideration of the advantages and disadvantages of each will be needed to recommend one approach over the other. [ABSTRACT FROM AUTHOR]