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Changes of renin-angiotensin system-related aminopeptidases in early stage Alzheimer's disease
journal contribution
posted on 2023-06-09, 02:48 authored by Paul Richard Gard, Sara Fidalgo, Isabelle Lotter, Cassandra Richardson, Nicolas Farina, Jennifer Rusted, Naji TabetNaji TabetActivities 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 from 45 AD patients at the start of the study, and again 13 months later (n = 37). The control group was 22 healthy, older, adults. Enzyme activity was 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 AD were not a ‘class effect’ for serum aminopeptidases but were idiosyncratic for the individual enzymes.
History
Publication status
- Published
File Version
- Accepted version
Journal
Experimental GerontologyISSN
0531-5565Publisher
ElsevierExternal DOI
Volume
89Page range
1-7Department affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-01-09First Open Access (FOA) Date
2018-01-08First Compliant Deposit (FCD) Date
2017-01-09Usage metrics
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