APOE and Alzheimer disease: A clear clue that links ageing and AD is that traditional GWAS have repeatedly demonstrated that APOE is the top genetic risk factor contributing to both late-onset AD17 and longevity,14,15 with the ɛ4 isoform being detrimental in both contexts, showing the highest risk for AD (with earlier age of onset among the late-onset AD cases)46 and the lowest odds for longevity.