Fig. 5: Replication.
a-b Linear PRS-AD associations with age-relative and absolute brain change in an independent adult lifespan sample (Lifebrain replication sample), using the four GWAS-derived scores, tested for progressively older age-ranges to ensure capture of ageing-specific effects (i.e., moving from left to right on the X-axis, the leftmost age-range represents the association across the full adult lifespan on average [30–88 years; N = 293], whereas the rightmost age-range shows the associations tested in only the oldest adults [60–88 years]). Univariate linear associations were tested for (a) left and right hippocampus, and (b) left and right amygdala. Significant associations at p < 0.05 (uncorrected) are depicted in colour (upper panels), with colours corresponding to the GWAS used to derive the four scores (Jansen, Kunkle, Lambert, Wightman). For associations that were significant at p < 0.05 (uncorrected), partial r2 of PRS-AD is shown (lower panels). For these, we retested the association after removing APOE (PRS-ADnoAPOE). Partial r2 of PRS-ADnoAPOE is depicted by a black cross if the association remained significant at p < 0.05 (uncorrected). c Multivariate linear PRS-AD association tests using PC1 of age-relative change across the top 50 brain features with accelerated change in AD (excluding hippocampal and amygdala volumes; PC1relChange; as in Fig. 4a, b). Datapoints show −log10 p-values for the association with PC1relChange, tested at progressively older age-ranges, for all four scores. Datapoint symbol corresponds to the GWAS used to derive the four scores (Jansen, Kunkle, Lambert, Wightman). d Standardized Betas in c as a function of age-range (inversed to be negative due to the non-directional nature of PCA). Dashed line indicates p = 0.05. e PC1 of absolute change across the top 50 brain features with accelerated change in AD (excluding hippocampal and amygdala volumes; maroon bar in Fig. 4a), plotted as a function of mean age across timepoints. Accelerated brain change in AD-accelerated features was evident around age 50–60. Note that since the y-axis represents change, the slope of the curve represents acceleration (see also Supplementary Fig. 14). Error bands and error bars depict 95% CI. Summary-level source data are provided as a Source Data file.
