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Angiotensin-III is Increased in Alzheimer's Disease in Association with Amyloid-β and Tau Pathology

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalJournal of Alzheimer's Disease
Volume58
Issue number1
Early online date3 May 2017
DOIs
DateAccepted/In press - 2 Mar 2017
DateE-pub ahead of print - 3 May 2017
DatePublished (current) - 3 May 2017

Abstract

Hyperactivity of the renin-angiotensin system (RAS) is associated with the pathogenesis of Alzheimer’s disease (AD) believed to be mediated by angiotensin-II (Ang-II) activation of the angiotensin type 1 receptor (AT1R). We previously showed that angiotensin-converting enzyme-1 (ACE-1) activity, the rate-limiting enzyme in the production of Ang-II, is increased in human postmortem brain tissue in AD. Angiotensin-III (Ang-III) activates the AT1R and angiotensin type-2 receptor (AT2R), but its potential role in the pathophysiology of AD remains unexplored. We measured Ang-II and Ang-III levels by ELISA, and the levels and activities of aminopeptidase-A (AP-A) and aminopeptidase-N (AP-N) (responsible for the production and metabolism of Ang-III, respectively) in human postmortem brain tissue in the mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59), for which we had previous measurements of ACE-1 activity, Aβ level, and tau pathology (also in the mid-frontal cortex). We found that both Ang-II and Ang-III levels were significantly higher in AD compared to age-matched controls and that Ang-III, rather than Ang-II, was strongly associated with Aβ load and tau load. Levels of AP-A were significantly reduced in AD but AP-A enzyme activity was unchanged whereas AP-N activity was reduced in AD but AP-N protein level was unchanged. Together, these data indicate that the APA/Ang-III/APN/Ang-IV/AT4R pathway is dysregulated and that elevated Ang-III could contribute to the pathogenesis of AD.

    Research areas

  • Alzheimer's disease, aminopeptidase-A, aminopeptidase-P, angiotensin-II, angiotensin-III, renin-angiotensin system

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via IOS Press at https://content.iospress.com/articles/journal-of-alzheimers-disease/jad161265 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 585 KB, PDF-document

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