Overall, the extended genetic analysis of a well-defined cohort of Italian EOAD patients showed that in cases without dominant pathogenic variants in PSEN1, PSEN2 and APP, there is an enrichment for multiple pathogenic/likely pathogenic variants in genes associated with risk factors for AD, covering 38% of our cohort, supporting the extreme genetic heterogeneity of EOAD. This evidence concerns the gene APP and Alzheimer disease.