Extended Data Fig. 1: Plasma eMTBR-tau243 changes by diagnosis and correlations with CSF MTBR-tau243 in the two pilot cohorts.

a,c, Levels of plasma eMTBR-tau243 by clinical diagnosis and Aβ status in the pilot BioFINDER-2 cohort (n = 108) (a) and the pilot Knight ADRC cohort (n = 55) (c). Differences in plasma eMTBR-tau243 levels by diagnostic groups were tested using ANOVA and the post hoc analyses were performed two-sided using. Boxplots summarize data distribution, showing the median (central line), interquartile range (box), and whiskers extending to 1.5 times the interquartile range. *, p < 0.05; **, p < 0.01; ***, p < 0.001. b,d, Associations between CSF MTBR-tau243 and plasma eMTBR-tau243 in BioFINDER-2 cohort (n = 108) (b) and the Knight ADRC cohort (n = 55) (d). CSF MTBR-tau243 in BioFINDER-2 and the Knight ADRC cohorts were analyzed by the previously reported immunoprecipitation method¹⁹ and the chemical extraction method²³, respectively. In the pilot BioFINDER-2 cohort, green dots color indicates global tau-PET positivity. In the pilot Knight-ADRC cohort, green dots color indicates Aβ-status positivity. For the scatter plots, linear regression lines (solid black) with 95% confidence intervals (shaded area) are also shown. All tests were two-sided. BioFINDER-2 pilot: AD+ vs. CU-: p < 0.001; AD+ vs. MCI + : p = 0.014; Knight-ADRC: AD+ vs CU-: p < 0.001; AD+ vs. CU + : p = 0.001; AD+ vs. very mild AD + : p = 0.005. Abbreviations: Aβ, amyloid β; AD + , Alzheimer’s disease dementia Aβ-positive; CU-, cognitively unimpaired Aβ-negative; CU + , cognitively unimpaired Aβ-positive; MCI + , mild cognitive impairment Aβ-positive; MTBR, microtubule-binding region.