APOE and Alzheimer disease: It is well known that the APOE ɛ4 allele is associated with amyloid accumulation, a process that emerges over decades and precedes overt clinical symptoms in AD.43 Current evidence suggests that APOE ɛ4 is not associated with suspected nonamyloid pathophysiology and primary age-related tauopathy,44,45 supporting that the APOE associations in this study are likely along the AD cascade.