APOE and Alzheimer disease: We identified 3 dimensions that are major drivers of the heterogeneity within AD: (1) risk factors, including sex, APOE, and age; (2) protective factors, including aspects such as cognitive reserve, brain resilience, and brain resistance; and (3) concomitant non-AD pathologies that together with amyloid (A) and tau-related pathology (T) may contribute to the neurodegeneration (N) seen in AD, which are formulated under the A/T/N framework for AD.35