However, under aberrant conditions, such as a significant reduction in NEP activity presumably caused by brain aging processes and AD development, the NEP-independent pathway(s) may be opened and Aβ1-42 may be processed by aminopeptidases or dipeptidyl peptidases, which are present in the extracellular milieu in the brain (Mentlein, 2004; Banegas et al, 2006; Hui, 2007; Khosla et al, 2022) (Figs 7 and S10). This evidence concerns the gene CPQ and Alzheimer disease.