Open AccessChanges with Age in the Activities of β‐Secretase and the Aβ‐Degrading Enzymes Neprilysin, Insulin‐Degrading Enzyme and Angiotensin‐Converting Enzyme
Author(s) -
Miners J. Scott,
Van Helmond Zoë,
Kehoe Patrick G.,
Love Seth
Publication year - 2010
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2010.00375.x
Subject(s) - insulin degrading enzyme , neprilysin , enzyme , chemistry , enzyme assay , endocrinology , prolyl endopeptidase , medicine , insulin , angiotensin converting enzyme , renin–angiotensin system , biochemistry , biology , blood pressure
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.