Peptidases, proteases and amyloid β-peptide catabolism

The formation of senile plaques containing amyloid βpeptides (Aβ peptides) as a major constituent plays a significant role in development of Alzheimer's disease. The concentration of Aβ peptides in the brain is determined by a combination of their rate of synthesis and their rate of clearance. Considerable effort has been expended in producing inhibitors of the β and γ secretases involved in the synthesis of the Aβ peptides. More recently interest in the mechanism of clearance of the Aβ peptides has emerged, as promoting Aβ peptide clearance represents an alternative therapeutic approach. It now appears that cleavage of Aβ peptide by peptidases and proteases represents the major mechanism of clearance. This review describes those peptidases and proteases implicated in Aβ peptide clearance, the evidence that these enzymes function in vivo, and how they may represent new therapeutic targets.