PSEN2 and familial Alzheimer disease: fAD on the other hand, is caused by specific mutations in Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) or Amyloid precursor protein (APP), affecting APP processing, thus supporting the currently widely accepted “Aβ cascade hypothesis.” APP can be processed through the amyloidogenic or the non-amyloidogenic pathway, where the former leads to production of amyloid beta (Aβ) peptides (Figure 1).