Trajectories of PiB PET (A,D), CSF Aβ42 (B, E), and Clinical Dementia Rating (CDR) sum of boxes (C,F) across variant groupings. In panels A-C, individual variants were categorized according to the protein domain affected by the underlying genetic variation. In panels D-F, PSEN1 pathogenic variant carriers were grouped based on whether the identified variant in PSEN1 was before or after codon 200. No significant differences between variant groupings were observed in CSF Aβ42 or in CDR sum of boxes (panels B, C, E, and F), but significant variant-dependent variations in amyloid PET signal were observed using both the domain- and codon-based groupings (A,D; Supplemental Figure 2). * denotes FDR corrected p ≤ 0.05 for each variant grouping by EYO interaction compared to all other pathogenic variant carriers; † denotes FDR corrected p ≤ 0.0001 for carriers of PSEN1 variants prior to codon 200 compared to those carriers of variants post codon 200.