Because Alzheimer’s disease is at least in part a cell cycle disease in which the generation and specific loss of aneuploid neurons in the brain accounts for 90% of the neuronal cell loss at autopsy, a person with trisomy 21 Down syndrome but with only two copies of the APP gene should not exhibit mosaic aneuploidy and may not develop Alzheimer’s disease. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.