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

• Blood pressure and the renin–angiotensin system are related to Alzheimer's disease.
• Several aminopeptidases catabolise circulating angiotensins and are modified in patients.
• Changes in renin–angiotensin system-regulating aminopeptidases show gender differences.
• Aminopeptidases are non-invasive biomarkers of the disease from the earliest stages.

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.