Extended Data Fig. 2: Sensitivity analyses testing the association of APOEε4 carriership and Aβ burden with tau accumulation including APOEε2 carriers.

(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 = 1.7, 95% CI 0.2 to 9.9, P = 0.582; Aβ+ APOEε4 noncarrier: OR = 1.7, 95% CI 0.3 to 9.6, P = 0.559; and Aβ+ APOEε4 carrier: OR = 21.4, 95% CI 3.7 to 159.8, P = 0.001; Supplementary Fig. 1b). (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 model 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 including individuals bearing the ε2 allele of the APOE gene who were excluded from the main analyses (70 CU older adults, 28 with MCI, and 9 with AD dementia). Abbreviations: AD = Alzheimer’s disease; 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.