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

Patrick Gavin Kehoe, Elliott Hibbs, Laura E Palmer, J Scott Miners*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

31 Citations (Scopus)
449 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number1
Early online date3 May 2017
Publication statusPublished - 3 May 2017


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


Dive into the research topics of 'Angiotensin-III is Increased in Alzheimer's Disease in Association with Amyloid-β and Tau Pathology'. Together they form a unique fingerprint.

Cite this