Renin-Angiotensin System and Alzheimer’s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives

Victor    Teatini    Ribeiro; Leonardo    Cruz    de Souza; Ana    Cristina    Simões e Silva
doi:10.2174/0929866527666191230103739
Abstract

New roles of the Renin-Angiotensin System (RAS), apart from fluid homeostasis and Blood Pressure (BP) regulation, are being progressively unveiled, since the discoveries of RAS alternative axes and local RAS in different tissues, including the brain. Brain RAS is reported to interact with pathophysiological mechanisms of many neurological and psychiatric diseases, including Alzheimer’s Disease (AD). Even though AD is the most common cause of dementia worldwide, its pathophysiology is far from elucidated. Currently, no treatment can halt the disease course. Successive failures of amyloid-targeting drugs have challenged the amyloid hypothesis and increased the interest in the inflammatory and vascular aspects of AD. RAS compounds, both centrally and peripherally, potentially interact with neuroinflammation and cerebrovascular regulation. This narrative review discusses the AD pathophysiology and its possible interaction with RAS, looking forward to potential therapeutic approaches. RAS molecules affect BP, cerebral blood flow, neuroinflammation, and oxidative stress. Angiotensin (Ang) II, via angiotensin type 1 receptors may promote brain tissue damage, while Ang-(1-7) seems to elicit neuroprotection. Several studies dosed RAS molecules in AD patients' biological material, with heterogeneous results. The link between AD and clinical conditions related to classical RAS axis overactivation (hypertension, heart failure, and chronic kidney disease) supports the hypothesized role of this system in AD. Additionally, RAStargeting drugs as Angiotensin Converting Enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) seem to exert beneficial effects on AD. Results of randomized controlled trials testing ACEi or ARBs in AD are awaited to elucidate whether AD-RAS interaction has implications on AD therapeutics.
Keywords: Renin-angiotensin system, Alzheimer’s disease, angiotensin II, angiotensin-(1-7), dementia, neuroinflammation, amyloid hypothesis.
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DOI https://dx.doi.org/10.2174/0929866527666191230103739	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305
Protein & Peptide Letters

Renin-Angiotensin System and Alzheimer’s Disease Pathophysiology: From the Potential Interactions to Therapeutic Perspectives

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