APOE ε4 is considered the most detrimental allele since it dose-dependently increases AD risk and decreases the age of disease onset.8–11 There is considerable evidence supporting the notion that APOE4 and APOE3 have vastly different effects on AD pathogenesis,1,12–14 with APOE4 worsening Aβ fibrillization and clearance,15–17 Tau phosphorylation and aggregation,18–23 and glial dysfunction14,24 relative to APOE3. Here, MAPT is linked to Alzheimer disease.