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Neurovascular and Cognitive failure in Alzheimer’s Disease: Benefits of Cardiovascular Therapy

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Abstract

Alzheimer’s disease (AD) is a multifactorial and multifaceted disease for which we currently have very little to offer since there is no curative therapy, with only limited disease-modifying drugs. Recent studies in AD mouse models that recapitulate the amyloid-β (Aβ) pathology converge to demonstrate that it is possible to salvage cerebrovascular function with a variety of drugs and, particularly, therapies used to treat cardiovascular diseases such as hypercholesterolemia and hypertension. These drugs can reestablish dilatory function mediated by various endothelial and smooth muscle ion channels as well as nitric oxide availability, benefits that result in normalized brain perfusion. These cerebrovascular benefits would favor brain perfusion, which may help maintain neuronal function and, possibly, delay cognitive failure. However, restoring cerebrovascular function in AD mouse models was not necessarily accompanied by rescue of cognitive deficits related to spatial learning and memory. The results with cardiovascular therapies rather suggest that drugs originally designed to treat cardiovascular diseases that concurrently restore cerebrovascular and cognitive function do so through their pleiotropic effects. Specifically, recent findings suggest that these drugs act directly on brain cells and neuronal pathways involved in memory formation, hence, working simultaneously albeit independently on neuronal and vascular targets. These findings may help select medications for patients with cardiovascular diseases at risk of developing AD with increasing age. Further, they may identify molecular targets for recovering memory pathways that bear potential for new therapeutic avenues.

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Authors and Affiliations

  1. Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill University, 3801 University Street, Suite 748, Montréal, QC, H3A 2B4, Canada

    Edith Hamel, Jessika Royea, Brice Ongali & Xin-Kang Tong

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  1. Edith Hamel
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  2. Jessika Royea
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  3. Brice Ongali
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  4. Xin-Kang Tong
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Correspondence to Edith Hamel.

Acknowledgements

Acknowledgements

The work reported in this review was supported by Grants (to E. H.) from the Canadian Institutes of Health Research (CIHR, MOP-84275 and MOP-126001), la Fondation des maladies du Coeur du Québec, and a Research on Aging FRQS-NSFC collaboration Grant.

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Hamel, E., Royea, J., Ongali, B. et al. Neurovascular and Cognitive failure in Alzheimer’s Disease: Benefits of Cardiovascular Therapy. Cell Mol Neurobiol 36, 219–232 (2016). https://doi.org/10.1007/s10571-015-0285-4

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