While apoE isoforms can directly affect Alzheimer’s neuropathology, including the accumulation of amyloid-β (Aβ) and tau, increasing evidence has demonstrated that apoE isoforms also contribute to cognitive function through AD neuropathology-independent pathways (Liu et al., 2013; M. Di Battista et al., 2016; Montagne et al., 2020; Yamazaki et al., 2020). The gene discussed is MAPT; the disease is Alzheimer disease.