PSEN2 and Alzheimer disease: One approach to address these challenges is to study individuals who carry an autosomal dominantly inherited AD (ADAD) mutation in the amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) gene that leads to increased relative production of the Aβ42 peptide throughout life and early brain Aβ plaque deposition11,12.