Multimodal, integrative, and systems-scale paradigms hold the potential to map clinical–biological trajectories of brain endophenotypes in cognitively healthy individuals at risk; for instance, in the context of AD, carriers of the apolipoprotein E (APOE) e4 allele, individuals with incipient Aβ/tau accumulation, or people reporting subjective memory complaints [5,53,62,151]. The gene discussed is APOE; the disease is Alzheimer disease.