Plasma renin–angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype

Puertas, María del Carmen; Martínez-Martos, José Manuel; Cobo, Manuela; Lorite, Pedro; Sandalio, Rosa María; Palomeque, Teresa; Torres, Marı́a Isabel; Carrera-González, María Pilar; Mayas, Marı́a Dolores; Ramírez-Expósito, María Jesús

doi:10.1016/j.exger.2013.03.002

Cited by 20 publications

(15 citation statements)

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“…In the study of Puertas et al (2013) the two groups were very closely matched, whilst in the current study the controls were approximately 6 years younger than the AD patients; Kuda et al state that the groups were age matched without giving any ages. Such an age difference in the current study may have obscured any differences in enzyme activity between the groups as there is evidence of increasing aminopeptidase activity with age (eg Ijima et al, 2002); any such age-related increase in enzyme activity might explain the failure to identify reduced aminopeptidase activity the older AD patients.…”

Section: Discussionmentioning

confidence: 87%

“…Such an age difference in the current study may have obscured any differences in enzyme activity between the groups as there is evidence of increasing aminopeptidase activity with age (eg Ijima et al, 2002); any such age-related increase in enzyme activity might explain the failure to identify reduced aminopeptidase activity the older AD patients. Although the patients of the current study were markedly older than those studied by Puertas et al (2013), by approximately 8 years, the MMSE scores (derived from ACE-R), however, were very similar, suggesting a comparable disease severity. Unlike the study of Puertas, the current study did not detect any significant relationship between enzyme activity and MMSE score, nor scores on any of the other, more sensitive, psychometric tests.…”

Section: Discussionmentioning

confidence: 89%

“…Aminopeptidase activity was determined by cleavage of leucyl-ß-naphthylamide and leucine-p-nitroanilde in the two studies respectively. Two other differences between the current study and that of Puertas (2013) were the use of serum rather than plasma, and the expression of enzyme activities relative to serum volume or plasma protein. Whilst for some proteins there are markedly different concentrations in serum and plasma, for example brain derived neurotrophic factor (240 amino acids) for which concentrations are 10-fold higher in serum than plasma (eg D 'Sa et al, 2012), the aminopeptidases (eg ApN: 967 amino acids, IRAP: 1024 amino acids) do not appear to differ in concentration between the two fluids (eg Fylling, 1964, Riad, 1966.…”

Section: Discussionmentioning

confidence: 99%

“…Kuda et al, (1997) reported that the activity of aminopeptidase A (ApA) but not aminopeptidase B (ApB) nor aminopeptidase N (ApN) was decreased in plasma from patients with Alzheimer's disease (AD). More recently Puertas et al (2013) reported that the activities of plasma ApA, ApB, ApN and IRAP were decreased in patients with early stage Alzheimer's disease (AD) compared to healthy, age-matched controls. The changes in ApA activity were seen in male patients only and there was no difference in the activity of aspartyl aminopeptidase between patients and controls.…”

Section: Introductionmentioning

confidence: 99%

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

Gard

Fidalgo

Lotter

et al. 2017

Experimental Gerontology

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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 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 MichaelisMenten 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.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Gard

Fidalgo

Lotter

et al. 2017

Experimental Gerontology

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“…IRAP has been confirmed as a regulator of oxytocin functions in the prostate11. It has been also involved in pathologies such as breast cancer and Alzheimer's disease121314.…”

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confidence: 99%

A PCR-RFLP method for detection of the LNPEP encoding human insulin-regulated aminopeptidase (IRAP) rs4869317 polymorphism

et al. 2016

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Background & objectives:Insulin regulated aminopeptidase (IRAP) has been related to certain pathologies such as breast cancer, Alzheimer's disease and septic shock. IRAP is encoded by the leucyl/cystinyl aminopeptidase (LNPEP) gene. The genetic variation in the LNPEP gene has been analyzed in relation with the mortality and vasopressin clearance in septic shock. The LNPEP rs4869317 SNP (single nucleotide polymorphism) was the most significantly associated SNP with vasopressinase activity, being TT genotype associated with increased mortality. The objective of the present study was to develop a simple method to allow a quick and affordable genotyping for the rs4869317 SNP of LNPEP gene.Methods:Blood DNA samples were obtained from randomly selected healthy volunteers (n=28). A pair of primers was designed to amplify an 834 bp region of the LNPEP gene containing the rs4869317 SNP. The two alleles (T or A) were detected by digestion of the PCR products with the PacI restriction endonuclease. This enzyme only cuts the PCR products when the adenine is present in the SNP.Results:All individuals showed RFPL (restriction fragment length polymorphism) fragments for the expected genotypes (TT, TA or AA). The methodology was validated by sequencing of the amplified DNAs from several ‘T/T’ and ‘A/A’ homozygotes and ‘T/A’ heterozygotes. The results from both methods showed agreement.Interpretation & conclusions:The PCR-RFLP is a simple and reliable method that allows a quick genotyping for the rs4869317 SNP of LNPEP gene. The study of this polymorphism could be useful in future investigations to analyze the role of genetic variants of IRAP in several physiological/pathological conditions.

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Sex Differences in the Genetic Architecture of Alzheimer’s Disease

et al. 2019

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Purpose of Review.-Summarize sex-specific contributors to the genetic architecture of Alzheimer's disease (AD). Recent Findings.-There are sex differences in the effects of Apolipoprotein E (APOE), genes along the APOE pathway, and genes along the neurotrophic signaling pathway in predicting AD. Reported sex differences are largely driven by stronger associations among females. Evidence also suggests that genetic predictors of amyloidosis are largely shared across sexes, while sex-specific genetic effects emerge downstream of amyloidosis and drive the clinical manifestation of AD. Summary.-There is a lack of comprehensive assessments of sex differences in genome-wide analyses of AD and a need for more systematic reporting a sex-stratified genetic effects. The emerging emphasis on sex as a biological variable provides an opportunity for transdisciplinary collaborations aimed at addressing major analytical challenges that have hampered advancements in the field. Ultimately, sex-specific genetic association studies represent a logical first step towards precision medicine.

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Plasma renin–angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype

Cited by 20 publications

References 58 publications

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

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

A PCR-RFLP method for detection of the LNPEP encoding human insulin-regulated aminopeptidase (IRAP) rs4869317 polymorphism

Sex Differences in the Genetic Architecture of Alzheimer’s Disease

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