title: 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 from 45 AD patients at the start of the study, and again 13months 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.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK. Electronic address: p.r.gard@brighton.ac.uk.
authors.forename: Paul Richard
authors.initials: PR
authors.lastname: Gard
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Fidalgo
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lotter
authors.affiliation: School of Psychology, University of Central Lancashire, Preston, UK.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Richardson
authors.affiliation: Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Farina
authors.affiliation: School of Psychology, University of Sussex, Brighton, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rusted
authors.affiliation: Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Naji
authors.initials: N
authors.lastname: Tabet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology*; D000626:Aminopeptidases / Q000097:blood* / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D012084:Renin-Angiotensin System
chemical_list: D000626:Aminopeptidases
keywords: Alzheimer's disease; Aminopeptidase A; Aminopeptidase B; Aminopeptidase N; Insulin-regulated aminopeptidase; Renin-angiotensin system