The apolipoprotein (APOE) ε4 gene is the strongest genetic risk factor of late-onset dementia and particularly Alzheimer disease.1,2 Homozygous carriers of the APOE ε4 allele have an absolute risk of 50% by age of 85 years to develop dementia due to Alzheimer disease, compared with less than 10% in noncarriers.3 Insight into the potential pathways that mediate the effect of APOE on cognitive decline and dementia is important to unravel pathophysiology and to identify potential therapeutic targets.4 This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.