In summary, our study, derived from a large national biomarker cohort, documents that a positive family history of AD is associated with an abnormal beta-amyloid and tau endophenotype prior to the onset of clinical AD in mildly symptomatic subjects, and that there are genetic influences embedded within FH beyond that due to ApoE4 that are most obvious in the MCI cohort. The gene discussed is APOE; the disease is Alzheimer disease.