APOE and early-onset autosomal dominant Alzheimer disease: Genome-wide association studies (GWASs) have highlighted multiple Alzheimer’s risk loci of small effect in addition to the major contributor, APOE.3-5 Polygenic risk scores (PRSs) are the weighted sum of these risk loci across the genome.6 By quantifying the genetic burden from numerous small loci, PRS can accurately predict Alzheimer’s Disease.7,8 However, as PRSs aggregate risk loci, it is not possible to make mechanistic interpretations.