Extended Data Fig. 3: Association of APOEε4 carriership and Aβ burden with tau accumulation in the subgroup of non-demented participants.

(a) Violin plot of temporal meta-ROI tau-PET SUVR change across groups. The horizontal line inside each box depicts the median, and box ends represent the 25th and 75th percentiles, with whiskers extending to 1.5 × interquartile range. The horizontal dashed line represents the threshold for tau accumulation. Groups were compared using two-sided analysis of covariance with Tukey’s multiple comparisons test. (b) The figure shows the ORs from logistic regression on being classified as tau accumulator. Only the concomitant presence of Aβ+ and APOEε4 carriership was associated with higher odds of being classified as tau accumulator (Aβ- APOEε4 noncarrier: reference group; Aβ- APOEε4 carrier: OR = 1.5, 95% CI 0.2 to 9.2, P = 0.696; Aβ+ APOEε4 noncarrier: OR = 0.9, 95% CI 0.1 to 7.8, P = 0.910; and Aβ+ APOEε4 carrier: OR = 18.8, 95% CI 2.0 to 228.7, P = 0.013; Supplementary Fig. 1c). (c) The scatter-plot displays the association between global Aβ-PET SUVR and temporal meta-ROI tau-PET SUVR change in APOEε4 noncarriers (blue) and carriers (red). The error bands indicate the 95% CI. Density plots along the x and y axes provide the data distribution. The β estimate and P value were computed from a linear regression assessing the interaction of APOEε4 status and global Aβ-PET burden on longitudinal tau-PET. Regressions were two-sided and adjusted for age, sex, diagnosis, and baseline tau-PET burden. The interaction model also accounted for APOEε4 status and global Aβ-PET burden main effects. Analyses were conducted in the subgroup of non-demented participants (62 CU older adults and 25 with MCI). Abbreviations: APOEε4 = apolipoprotein E ε4; Aβ = amyloid-β; CI = confidence interval; CU = cognitively unimpaired; MCI = mild cognitive impairment; OR = odds ratio; PET = positron emission tomography; ROI = region of interest; SUVR = standardized uptake value ratio.