Changes of renin-angiotensin system-related aminopeptidases in early stage Alzheimer's disease

Abstract

Activities of aminopeptidases A, B, and N (ApA, ApB & ApN) and insulin-regulated aminopeptidase (IRAP) have
been seen to be decreased amongst patients with Alzheimer's disease (AD). All of these enzymes are involved
with the brain renin-angiotensin system which is believed to be involved with learning and memory. This
study aimed to explore the time course and the mechanisms underlying these changes.
Serum samples were collected from45 AD patients at the start of the study, and again 13 months later (n=37).
The control groupwas 22 healthy, older, adults. Enzyme activitywas determined at two substrate concentrations
to allow Michaelis-Menten analysis of the enzyme activity.
The results indicated that there was decreased activity of ApA, ApB and ApN amongst AD patients but no difference
in serum IRAP activity. There were no associations between enzyme activity and age, gender nor scores on
psychomotor tests.
Consideration of the data for the two time points for AD patients showed that the changes in ApB occurred at an
early stage of the disease and persisted, whilst those of ApA and ApN only became apparent at later stages of the
disease. Although differences in Michaelis-Menten parameters were not statistically significant, consideration of
the values suggested that the decrease in ApB activity may be a result of changes in enzyme protein conformation,
whilst that of ApN may be a consequence of decreased enzyme expression. Importantly, the different
time courses of the effects and the differential changes in enzyme affinity and expression indicated that the observed
changes with progression of ADwere not a ‘class effect’ for serumaminopeptidases butwere idiosyncratic
for the individual enzymes.