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Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is multifactorial in nature. Yet, despite being the most common form of dementia in the elderly, AD’s primary cause remains unknown. As such, there is currently little to offer AD patients as the vast majority of recently tested therapies have either failed in well-controlled clinical trials or inadequately treat AD. Recently, emerging preclinical and clinical evidence has associated the brain renin angiotensin system (RAS) to AD pathology. Accordingly, various components of the brain RAS were shown to be altered in AD patients and mouse models, including the angiotensin II type 1 (AT1R), angiotensin IV receptor (AT4R), and Mas receptors. Collectively, the changes observed within the RAS have been proposed to contribute to many of the neuropathological hallmarks of AD, including the neuronal, cognitive, and vascular dysfunctions. Accumulating evidence has additionally identified antihypertensive medications targeting the RAS, particularly angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), to delay AD onset and progression. In this review, we will discuss the emergence of the RAS’s involvement in AD and highlight putative mechanisms of action underlying ARB’s beneficial effects that may explain their ability to modify the risk of developing AD or AD progression. The RAS may provide novel molecular targets for recovering memory pathways, cerebrovascular function, and other pathological landmarks of AD.

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Funding

The work from our laboratory referred in this review was funded by grants from the Canadian Institute of Health Research (MOP 126001), the Heart and Stroke Foundation of Québec, and the Alzheimer Society of Canada. JR received studentships from the Canadian Vascular Network-Hypertension and les Fonds de Recherche du Québec - Santé (FRQS).

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  1. Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, 3801 University Street, Montréal, QC, H3A 2B4, Canada

    Jessika Royea & Edith Hamel

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  1. Jessika Royea
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  2. Edith Hamel
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Correspondence to Edith Hamel.

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Royea, J., Hamel, E. Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets. GeroScience 42, 1237–1256 (2020). https://doi.org/10.1007/s11357-020-00231-y

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