BACE1 and Alzheimer disease: The most significant of these are: (i) the cholinergic hypothesis which postulates that the cognitive decline can be linked to a decrease in the amount of the neurotransmitter acetylcholine (ACh)5 and (ii) the amyloid hypothesis which instead ascribes AD symptoms to the Amyloid Precursor Protein (APP) that undergoes a sequential post-translational proteolysis/processing by β-secretase 1 (BACE-1) and γ-secretase leading to the formation of hydrophobic Aβ peptide fibrils that readily accumulate and deposit on neuritic plaques in the gray matter of the brain.6