ABSTRACT
Alterations in blood pressure and components of the renin-angiotensin system (RAS) contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. Aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase N (APN) and aminopeptidase B (APB) catabolise circulating angiotensins, whereas insulin-regulated aminopeptidase (IRAP) has been described as the AT4 receptor. We have found in AD patients a significant decrease of APA activity in men but not in women, and of APN, APB and IRAP in both genders, when compared with control subjects. No changes were found in ASAP activity. Also, APN, APB and IRAP but not APA correlated with the Mini-Mental test, but no relationship with APOE genotype was found. We conclude that several components of the RAS are modified in AD patients, with gender differences. Furthermore, ROC analysis indicates that APN, APB and IRAP activities could be useful non-invasive biomarkers of AD from the earliest stages.
Subject(s)
Alzheimer Disease/enzymology , Alzheimer Disease/genetics , Aminopeptidases/metabolism , Apolipoproteins E/genetics , Renin-Angiotensin System/genetics , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Apolipoproteins E/metabolism , CD13 Antigens/metabolism , Cognition/physiology , Cystinyl Aminopeptidase/metabolism , Early Diagnosis , Female , Genotype , Glutamyl Aminopeptidase/metabolism , Humans , Male , Neuropsychological Tests , Receptors, Angiotensin/metabolism , Sex FactorsABSTRACT
BACKGROUND: Angiotensin peptides play roles in brain tumor infiltration and associated angiogenesis. MATERIALS AND METHODS: We explored the roles of soluble and membrane-bound forms of renin-angiotensin system-regulating aminopeptidase N (APN)-, aminopeptidase B (APB)-, glutamate aminopeptidase- and aspartate aminopeptidase (AspAP)-specific activities on tumor growth in the rat C6 glioma model with implantation into the subcutaneous abdomen of Wistar rats, evaluating these activities as biological markers. The tumor volume was assessed for three weeks and a sample of tumor was obtained every seven days to obtain the soluble and membrane-bound fraction, in order to assay enzyme activities fluorometrically using their corresponding aminoacyl-ß-naphthylamide as substrates. RESULTS: We found a time-dependent decrease in soluble and membrane-bound APN and APB. Soluble AspAP increases with tumor growth in a time-dependent manner. CONCLUSION: Although gliomas are heterogeneous tissues, angiotensin peptides are involved in this model of tumor growth and their role could be analyzed through their corresponding regulatory proteolytic enzymes.
