Neurochemical Research

, Volume 22, Issue 1, pp 49–56

Degradation of Alzheimer's ß-Amyloid Protein by Human and Rat Brain Peptidases: Involvement of Insulin-Degrading Enzyme

  • J. R. McDermott
  • A. M. Gibson

DOI: 10.1023/A:1027325304203

Cite this article as:
McDermott, J.R. & Gibson, A.M. Neurochem Res (1997) 22: 49. doi:10.1023/A:1027325304203


We examined the degradation of Alzheimer's ß-amyloid protein (1–40) by soluble and synaptic membrane fractions from post mortem human and fresh rat brain using HPLC. Most of the activity at neutral pH was in the soluble fraction. The activity was thiol and metal dependent, with a similar inhibition profile to insulin-degrading enzyme. Immunoprecipitation of insulin-degrading enzyme from the human soluble fraction using a monoclonal antibody removed over 85% of the ß-amyloid protein degrading activity. Thus insulin-degrading enzyme is the main soluble ß-amyloid degrading enzyme at neutral pH in human brain. The highest ß-amyloid protein degrading activity in the soluble fractions occurred between pH 4–5, and this activity was inhibited by pepstatin, implicating an aspartyl protease. Synaptic membranes had much lower ß-amyloid protein degrading activity than the soluble fraction. EDTA (2mM) caused over 85% inhibition of the degrading activity but inhibitors of endopeptidases −24.11, −24.15, −24.16, angiotensin converting enzyme, aminopeptidases, and carboxypeptidases had little or no effect.

ß-amyloid protein Alzheimer's disease insulin-degrading enzyme human brain cathepsin D 

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • J. R. McDermott
    • 1
  • A. M. Gibson
    • 1
  1. 1.MRC Neurochemical Pathology UnitNewcastle General HospitalNewcastle upon TyneUK

Personalised recommendations