Fig. 4: ADNI-derived features applied to the healthy adult lifespan.

a Top brain features for classifying AD-long from NC-long individuals in ADNI data based on age-relative change. Coloured bars indicate feature selections across which we calculated PC1, and link with the subsequent plotted data in (b–e). b Linear PRS-AD associations in the LCBC healthy adult lifespan sample using PC1 of age-relative change across the top 50 features with accelerated change in AD (excluding hippocampal and amygdala volumes); PC1^relChange; maroon bar in (a). Datapoints show -log10 p-values for PRS-AD associations with PC1^relChange_, tested at progressively older age-ranges, for all four scores. Dashed line indicates p = 0.05, and black stroke depicts significant PRS-AD associations at p < 0.05 (uncorrected). Datapoints above the dotted line are significant at p(FDR) < 0.05. Datapoint symbol corresponds to the GWAS used to derive the four scores (Jansen, Kunkle, Lambert, Wightman). For associations surviving FDR-correction (across 144 two-sided tests), partial r² of PRS-AD is shown (lower panel). Where the association survived correction, we retested it after removing APOE (PRS-AD^noAPOE). Partial r² of PRS-AD^noAPOE is depicted by a black cross if the FDR-corrected association remained significant at p < 0.05. c Standardized PRS-AD betas in b as a function of age-range (inversed to be negative due to the non-directional nature of PCA). d PC1 of absolute change across the top 50 brain features with accelerated change in AD (excluding hippocampal and amygdala volumes); maroon bar in (a) as a function of mean age (across timepoints). Accelerated brain change in AD-accelerated features was evident between ages 50–60. Note that since the y-axis represents change, the slope of the curve represents acceleration (see also Supplementary Fig. 14). e Linear PRS-AD-change associations using a PCA-based sliding window analysis within the age-range 50–89 years. Colours and order correspond to the coloured bars in (a). Dashed line indicates p = 0.05, and datapoints with black stroke depict significant PRS-AD associations at p < 0.05 (uncorrected). Datapoints above the dotted line are significant at p(FDR) < 0.05. For associations surviving FDR-correction, partial r² of PRS-AD is shown (lower panel). Error bands and error bars depict 95% CI. lh left hemisphere, rh right hemisphere, vol volume (subcortical), int intensity (subcortical), w–g grey/white matter contrast, cc corpus callosum, DC diencephalon, csf cerebrospinal fluid. Subcortical features (aseg atlas) are delineated with “.”, whereas cortical features (aparc atlas) are delineated with “_”. Summary-level source data are provided as a Source Data file.