Fig. 2: CSF dynamics across estimated AD-pathological PET positivity in years.

CSF biomarker abnormality against estimated Aβ-PET positivity in years, with onset set at CL = 20 and estimated tau-PET positivity in years, with onset set at temporal META-ROI = 1.36 SUVR. PET-positivity onset is indicated with the black dotted line. A Illustrates changes in z-scored p-tau 217 forms (ratio: %p-tau217; phosphorylated p-tau: p-tau; and the non-phosphorylated reference epitope: np-tau 212–221), based on the mean and standard deviation of the cognitively unimpaired amyloid-negative cases. Shaded area’s indicate the 95% confidence interval. While %p-tau217 plateaus at higher AD pathological burden, phosphorylated p-tau217 shows steep continued increase in abnormality. This effect is also apparent, thought to a lesser extent, in the reference epitope np-tau212. B Illustrates the behavior of MTBR-tau243 and tau burden in PET regions-of-interest (ROIs) across chronology measures. Correcting MTBR-tau243 for CSF dynamics by means np-tau212 (the reference epitope of p-tau217) did not improve its association with intermediate and late tau ROIs, rather it resulted in a closer association with tau burden in early tau-accumulating (Braak I–II) regions. Red dotted line for z-score figures illustrates the 1.96 SD from the reference population. For all figures, the solid/dashed line illustrates the mean population trajectory, while the shaded area’s indicate the 95% confidence interval.