The role of APOE4 in neurological disease is certainly broader than the clearance or response to misfolded proteins, including Aβ and tau; for example, APOE receptors play diverse roles in brain physiology independent of Aβ (Holtzman et al., 2012) and APOE4 carriers may be susceptible to disorders that do not involve proteinopathy, such as chemotherapy-induced cognitive dysfunction (Mandelblatt et al., 2018; Speidell et al., 2019). Here, APOE is linked to nervous system disorder.