Logically, it is assumed that the protective effect of APOE2 is the opposite of APOE4. The protective effect is reflected in a low prevalence of APOE2 alleles in AD patient cohorts (Talbot et al, 1994; West et al, 1994; Reiman et al, 2020) and reduction of Aβ plaque load in APOE2 carriers (Chiang et al, 2010; Grothe et al, 2017; Kantarci et al, 2012; Nagy et al, 1995; Polvikoski et al, 1995; Serrano-Pozo et al, 2015). The gene discussed is APOE; the disease is Alzheimer disease.