Still, APOE remains the strongest risk factor in individuals ≥80 years old.58 Thus, the age-dependent heterogeneity of APOE is likely to be compounded by a survivor bias: individuals with a very late onset despite carrying APOE-e4 might harbour protective variants,60 such as KLOTHO-VS, where a protective effect on amyloid deposition and Alzheimer’s disease was observed in only 60- to 80-year-olds, but not in the 80+ group.57,61. This evidence concerns the gene KL and early-onset autosomal dominant Alzheimer disease.