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Keywords:

  • Alzheimer's disease;
  • ACE;
  • BACE-1;
  • β-secretase;
  • neprilysin;
  • IDE;
  • normal ageing

Abstract

We recently found that insoluble Aβ increases, but soluble Aβ decreases with age in normal brains. We now report the changes in activities of β-secretase (BACE-1) and Aβ-degrading enzymes with age, and their relationships to concentrations of soluble and insoluble Aβ. We measured BACE-1 activity and the levels and activities of neprilysin (NEP), insulin-degrading enzyme (IDE) and angiotensin-converting enzyme (ACE) in normal control brains (16 years–95 years). We also compared the measurements to those in AD. BACE-1 activity correlated closely with age in controls and was significantly higher in AD. In controls, NEP and IDE activities (but not protein levels) increased with age but ACE activity and level did not. BACE-1 activity correlated directly with insoluble but inversely with soluble Aβ. IDE activity correlated directly with insoluble Aβ and NEP activity was inversely related to soluble Aβ. ACE level correlated directly with insoluble and inversely with soluble Aβ in controls but not AD. Both Aβ-synthesizing and -degrading enzyme activities increase with age, coinciding with declining soluble Aβ and increasing insoluble Aβ. Further research is needed to establish whether these changes in enzyme activity and Aβ levels are causally related and if so how.