We hypothesized that a GWAS of brain β-amyloid burden in APOEε3/ε3 individuals would uniquely capture genetic variation associatedwith an early pathophysiologic event in AD, which is now being targeted by newdisease-modifying therapies.20 Tothese data, we applied a genetic risk score (GRS) framework to generate and validatean aggregate measure of genetic susceptibility to amyloidosis, relevant to the largeproportion of the population not carrying the APOE ε4 orε2 alleles. This evidence concerns the gene APOE and Alzheimer disease.