The renin-angiotensin system and antihypertensive drugs in Alzheimer's disease: current standing of the angiotensin hypothesis?

Patrick G. Kehoe*, Peter A. Passmore

*Corresponding author for this work

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

52 Citations (Scopus)

Abstract

There is an urgent need to improve upon Alzheimer's disease (AD) treatments. Limitations of existing drugs are that they target specific downstream neurochemical abnormalities while the upstream underlying pathology continues unchecked. Preferable treatments would be those that can target a number of the broad range of molecular and cellular abnormalities that occur in AD such as amyloid-β (Aβ) and hyperphosphorylated tau-mediated damage, inflammation, and mitochondrial dysfunction, as well more systemic abnormalities such as brain atrophy, impaired cerebral blood flow (CBF), and cerebrovascular disease. Recent pre-clinical, epidemiological, and a limited number of clinical investigations have shown that prevention of the signaling of the multifunctional and potent vasoconstrictor angiotensin II (Ang II) may offer broad benefits in AD. In addition to helping to ameliorate co-morbid hypertension, these drugs also likely improve diminished CBF which is common in AD and can contribute to focal Aβ pathology. These drugs, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor antagonists (ARAs) may also help deteriorating cognitive function by preventing Ang II-mediated inhibition of acetylcholine release as well as interrupt the upregulation of deleterious inflammatory pathways that are widely recognized in AD. Given the current urgency to find better treatments for AD and the relatively immediate availability of drugs that are already widely prescribed for the treatment of hypertension, one of the largest modifiable risk factors for AD, this article reviews current knowledge as to the eligibility of ACE-inhibitors and ARAs for consideration in future clinical trials in AD.
Original languageEnglish
Pages (from-to)S251-S268
Number of pages18
JournalJournal of Alzheimer's Disease
Volume30 Suppl 2
DOIs
Publication statusPublished - 2012

Keywords

  • cognitive decline
  • MILD COGNITIVE IMPAIRMENT
  • degradation
  • CEREBROVASCULAR-DISEASE
  • treatment
  • Alzheimer's disease
  • dementia
  • CONVERTING ENZYME-INHIBITORS
  • ACE-INHIBITORS
  • antagonist
  • A-BETA
  • amyloid-beta protein precursor
  • VASCULAR RISK-FACTORS
  • vascular
  • INSERTION-DELETION POLYMORPHISM
  • CEREBROSPINAL-FLUID LEVELS
  • angiotensin
  • hypertension
  • AMYLOID-BETA-PEPTIDE
  • amyloid-beta
  • BLOOD-BRAIN-BARRIER
  • Acetylcholine

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