In this multi-site study, the NODDI model is applied to characterize the effects of APOE ɛ4 and its interactions with age and education on cortical microstructural changes in cognitively normal individuals recruited from the PREVENT-Dementia35 and ALFAprojects.36 Both PREVENT-Dementia and ALFA are prospective observational cohort studies with the overarching goal of clarifying the pathophysiology and pathogenic factors occurring during the preclinical phase of Alzheimer’s disease. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.