Fig. 1: PET-based Braak staging captures variability in magnitude and topography of pathological tau.

a, Average [¹⁸F]MK6240 SUVRs across the whole brain for all participants grouped according to PET-based Braak stage. Individuals at stage 0 did not have detectable tau abnormality in regions comprising any Braak stage. At stage I, tau abnormality is confined to the transentorhinal cortex. Braak stages V and VI are characterized by high magnitude of tau pathology, with stage VI extending to primary sensory cortices. b, Regional accumulation of tau-PET conforms to hierarchical histopathological tau staging model. Higher levels of tau-PET SUVR in the transentorhinal cortices are observed at all subsequent stages (family-wise error (FWE)-corrected P < 0.001 for all). In the entorhinal and hippocampal cortices (Braak II regions), tau-PET is abnormal only in individuals assigned to PET-based Braak stage II and above and increased with advancing PET-based Braak stage. Overall, cortical regions remain largely spared until the corresponding Braak stage is reached. Only individuals assigned to stage VI had statistically different tau-PET SUVR in regions comprising Braak VI. Dashed lines represent stage-specific cutoffs for tau-PET in each Braak stage. Group means are represented by shapes, and error bars represent standard deviation. Stage I is represented by the purple circle, stage II is represented by the blue square, stage III is represented by the green triangle, stage IV is represented by the orange inverted triangle, stage V is represented by the hollow purple circle and stage VI is represented by the hollow blue square. Successive Braak stages are connected by a solid line, which carries the color of the previous stage. ***P < 0.001; two-sided analysis of variance (ANOVA) corrected for multiple comparisons using Dunnett’s correction (n = 324). c, Longitudinal stability and progression of Braak stage. Percentages along the diagonal indicate proportion of individuals at each Braak stage who did not change Braak stage over the follow-up period. Deviations from the diagonal indicate a change in Braak stage; percentages above the diagonal midline indicate Braak stage progression, and percentages below the diagonal midline likely represent misclassifications. d, Stage-specific associations between amyloid-β positivity and PET-based Braak stage progression. Aβ, amyloid-β; NS, not significant.