Regulation of amyloid β-peptide levels by enzymatic degradation

It is generally accepted that amyloid β peptides (Aβ) play a significant role in the etiology of Alzheimer's disease. The Aβ peptides are produced by the sequential cleavage of an amyloid precursor protein by a β secretase followed by cleavage by a γ secretase. The clearance of Aβ appears to be due primarily by the action of one or more peptidases. An imbalance between the rate of synthesis and the rate of clearance of Aβ is now considered a possible contributor to the onset of Alzheimer's disease. This review focuses on peptidases that have been proposed to contribute to Aβ catabolism and discusses the evidence for their participation in Aβ peptide clearance in vivo.