APOE and Alzheimer disease: Moreover, the age of AD onset scales inversely with APOE ε4 allele dose, whereby each additional ε4 allele shifts the individual toward a younger age of disease manifestation (estimated 2–5 or 5–10 yr earlier for one or two copies of the ε4 allele, respectively, relative to the lower risk group) (Corder et al, 1993; van der Lee et al, 2018; Yamazaki et al, 2019).