The full length APP, includes a signalling sequence, a largeextramembraneous sequence and the crucial membrane spanning domainfollowed by a short cytoplasmic tail.• The nonpathological cleavage occurs between Lys687-Leu688 by the α-secretase.• While this dominating event leaves the APP behind for the β-secretase,which is one of the two culprits in β amyloid formation.• γ-secretase is involved in both amyloidosis and non-amyloidosisprocessing. 39Non-Amyloidosis Amyloidosis