On the other C-terminal side of APP, γ-secretase (in both amyloidogenic and non-amyloidogenic pathways) also generate the “APP intracellular domain” (AICD), that has been reported to modulate the transcription of several genes (including APP itself, BACE-1 and the Aβ-degrading enzyme neprilysin), to regulate apoptosis and contribute to AD pathogenesis (Octave et al., 2013). Here, APP is linked to Alzheimer disease.