APOE and Alzheimer disease: These included FBXO21, which in mouse models has beendemonstrated to influence ubiquitination of structures important for brainβ-amyloid clearance.44Overall, our results support a broader model for genetic risk stratification foramyloid deposition in the general population, whereby APOEε4 and the non-APOE amyloid GRS exert robust butsubpopulation-specific (i.e., ε4-present distinct from ε4-absent)effects while other factors including APOE ε2 and additionalcase-control AD risk alleles may more modestly influence amyloid accumulation inthese states (Figure 3).