Arboleda-Velasquez et al. identified an individual with both an autosomal dominant AD mutation in PSEN1 (presenilin 1, E280A) and two alleles of a rare mutation within APOE-ε3, called the Christchurch mutation (APOE3ch, p.R136S), who experienced a multi-decades-long delay in the onset of cognitive symptoms despite having widespread amyloid deposition throughout the brain as measured by PET. Here, PSEN1 is linked to Alzheimer disease.