Genetic studies have successfully identified multiple genes and pathways associated with AD pathogenesis, including rare mutations in amyloid precursor protein (APP)3,4, presenilin 1 (PSEN1)5, and presenilin 2 (PSEN2)6 that cause autosomal dominant AD (ADAD), mainly by driving aberrant Aβ production in support of the amyloid cascade hypothesis7. This evidence concerns the gene APP and Alzheimer disease.