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The coming of age of the angiotensin hypothesis in Alzheimer's disease: Progress toward disease prevention and treatment?

Research output: Contribution to journalReview article

Original languageEnglish
Pages (from-to)1443-1466
Number of pages24
JournalJournal of Alzheimer's Disease
Volume62
Issue number3
Early online date13 Mar 2018
DOIs
DateAccepted/In press - 15 Jan 2018
DateE-pub ahead of print - 13 Mar 2018
DatePublished (current) - Mar 2018

Abstract

There is wide recognition of a complex association between midlife hypertension and cardiovascular disease and later development of Alzheimer's disease (AD) and cognitive impairment. While significant progress has been made in reducing rates of mortality and morbidity due to cardiovascular disease over the last thirty years, progress towards effective treatments for AD has been slower. Despite the known association between hypertension and dementia, research into each disease has largely been undertaken in parallel and independently. Yet over the last decade and a half, the emergence of converging findings from pre-clinical and clinical research has shown how the renin angiotensin system (RAS), which is very important in blood pressure regulation and cardiovascular disease, warrants careful consideration in the pathogenesis of AD. Numerous components of the RAS have now been found to be altered in AD such that the multifunctional and potent vasoconstrictor angiotensin II, and similarly acting angiotensin III, are greatly altered at the expense of other RAS signaling peptides considered to contribute to neuronal and cognitive function. Collectively these changes may contribute to many of the neuropathological hallmarks of AD, as well as observed progressive deficiencies in cognitive function, while also linking elements of a number of the proposed hypotheses for the cause of AD. This review discusses the emergence of the RAS and its likely importance in AD, not only because of the multiple facets of its involvement, but also perhaps fortuitously because of the ready availability of numerous RAS-acting drugs, that could be repurposed as interventions in AD.

    Research areas

  • ACE, Acetylcholine, Alzheimer's disease, Amyloid-β, Angiotensin, Cognitive decline, Dementia, Drug repurposing, Epidemiology, Hypertension, Treatment, Vascular

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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/jad171119 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 858 KB, PDF-document

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