Findings implicate differential regulation of disease- and aging-related cytoarchitectural changes by APOE genotype, such that APOE4 carriers undergo entorhinal neurodegeneration in preclinical and prodromal AD, with age-related striatal changes, whereas APOE4 non-carriers present with age-related entorhinal cortex microstructural abnormalities and striatal injury accompanying cognitive impairment. Here, APOE is linked to Alzheimer disease.