Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states

Biochim Biophys Acta. 2016 Jun;1860(6):1281-90. doi: 10.1016/j.bbagen.2016.03.010. Epub 2016 Mar 8.


To enhance our understanding of the potential therapeutic utility of insulin-degrading enzyme (IDE) in Alzheimer's disease (AD), we studied in vitro IDE-mediated degradation of different amyloid-beta (Aβ) peptide aggregation states. Our findings show that IDE activity is driven by the dynamic equilibrium between Aβ monomers and higher ordered aggregates. We identify Met(35)-Val(36) as a novel IDE cleavage site in the Aβ sequence and show that Aβ fragments resulting from IDE cleavage form non-toxic amorphous aggregates. These findings need to be taken into account in therapeutic strategies designed to increase Aβ clearance in AD patients by modulating IDE activity.

Keywords: Aggregation; Alzheimer's disease; Amyloid-beta; Aβ cleavage; Insulin-degrading enzyme; Neprilysin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Insulysin / physiology*
  • Molecular Sequence Data
  • Protein Aggregates*


  • Amyloid beta-Peptides
  • Protein Aggregates
  • Insulysin