Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Tau positron emission tomography (PET) staging is increasingly used to stratify Alzheimers disease (AD), yet cross-tracer interchangeability remains unestablished. In a prospective head-to-head study of 682 individuals across the aging-to-AD continuum, we compared tau PET Braak staging derived from [18F]Flortaucipir and [18F]MK6240. While both tracers showed high internal adherence to hierarchical Braak patterns (89-92%), cross-tracer agreement was limited (43%, weighted κ = 0.54) and fell to 14-23% at early-to-intermediate stages, a key window for therapeutic intervention. Discordance was strongly directional: in over 90% of discordant cases [18F]MK6240 assigned a higher stage, on average approximately one stage above [18F]Flortaucipir. [18F]MK6240 upstaging was associated with greater Aβ burden, adverse plasma biomarker profiles, and worse cognitive performance. Stage-frequency benchmarking against an external neuropathological cohort (N = 4,422) revealed that PET staging lags neuropathology by ~2 Braak stages for [18F]MK6240 and ~3 for [18F]Flortaucipir in the early phases of disease, with progressive convergence at later stages. Tau PET Braak staging is internally coherent within tracers but not interchangeable across them, with [18F]MK6240 systematically assigning higher stages than [18F]Flortaucipir. This biologically meaningful discordance, most pronounced at early stages, has direct implications for patient selection and staging for clinical trials and practice, necessitating tracer-aware harmonization strategies.
Source: medRxiv
Authors: Andreia Rocha, Carolina Soares, Marina Scoop Medeiros, Emma Ruppert, Arthur C. Macedo, Firoza Z. Lussier, Guilherme Povala, Bruna Bellaver, Pamela Cristina Lukasewicz Ferreira, Guilherme Bauer-Negrini, Livia Amaral, Matheus Rodrigues, Markley Oliveira-Junior, Rayan Mroue, Alvaro de Oliveira Franco, Cecile Tissot, Joao Pedro Ferrari-Souza, Nesrine Rahmouni, Jeffrey L. Evelhoch, Tobey J. Betthauser, Dana L. Tudorascu, Thomas K Karikari, Joseph C. Masdeu, Juan Fortea, David N. Soleimani-Meigooni, Val Lowe, Hwamee Oh, Belen Pascual, Brian A. Gordon, Pedro Rosa-Neto, Suzanne Baker, Tharick A. Pascoal, HEAD Study
Institutions: University of Pittsburgh, McGill University, Lawrence Berkeley National Laboratory, Hospital Moinhos de Vento, University of Wisconsin–Madison, Houston Methodist Research Institute, Hospital de Sant Pau, University of California, San Francisco, Mayo Clinic, Brown University, Washington University in St. Louis
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225199907