Additionally, the sequential cleavage of APP by BACE1 [43, 44] and γ-secretase (a complex composed of presenilin, nicastrin, Aph1 and Pen2) to Aβ [45, 46] is central to the pathophysiology of AD and is likely to play an early role in cognitive dysfunction. The gene discussed is BACE1; the disease is Alzheimer disease.