Importantly, the estimate of age at onset and the variability range was similar to that described in families with APP duplications (52.2; 95% CI, 49.9-54.4).20 This agrees with the concept that dementia in Down syndrome is primarily driven by the extra copy of the APP gene, which is both sufficient and necessary to cause Alzheimer disease pathology and symptoms.8,12. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.