PSEN1 and early-onset autosomal dominant Alzheimer disease: For autosomal dominant early-onset Alzheimer's disease (EOAD), mutations in the APP, presenilin 1 (PSEN1), or presenilin 2 (PSEN2) gene sequence are a major risk factor, while the APOE4 allele is a major risk factor for late-onset Alzheimer's disease (LOAD) [82].