Am J Cardiovasc Dis 2013;3(4):197-226

Review Article
Evidence of endothelial dysfunction in the development of Alzheimer’s
disease: Is Alzheimer’s a vascular disorder?

Rory J Kelleher, Roy L Soiza

School of Medical Sciences, University of Aberdeen, United Kingdom; Health Services Research Unit, University of
Aberdeen, Aberdeen, United Kingdom; Department of Medicine for The Elderly, NHS Grampian, Aberdeen, United Kingdom

Received October 7, 2013; Accepted October 26, 2013; Epub November 1, 2013; Published November 15, 2013

Abstract: The etiology of Alzheimer’s disease (AD) remains unclear. The emerging view is that cerebrovascular
dysfunction is a feature not only of cerebrovascular diseases, such as stroke, but also of neurodegenerative conditions,
such as AD. In AD, there is impaired structure and function of cerebral blood vessels and cells in the neurovascular unit.
These effects are mediated by vascular oxidative stress. Injury to the neurovascular unit alters cerebral blood flow
regulation, depletes vascular reserves, disrupts the blood-brain barrier and reduces the brain’s repair capacity. Such injury
can exacerbate the cognitive dysfunction exerted by incident ischemia and coexisting neurodegeneration. This article
summarises data regarding cardiovascular risk factors, vascular abnormalities and brain endothelial damage in AD. In
view of accumulating evidence of vascular pathology in AD, we also review the literature (MEDLINE, EMBASE) for clinical
evidence of impaired endothelial function in AD. A total of 15 articles investigating endothelial dysfunction in AD were
identified. 10 of these articles showed impaired endothelial function in AD patients. The current literature suggests
endothelial dysfunction may be involved in the pathogenesis of AD. This aspect of AD pathology is particularly interesting in
view of its potential for therapeutic intervention. Future research on endothelial function in AD should concentrate on
population-based analysis and combine multiple methods to evaluate endothelial function. (AJCD1310002).

Keywords: Alzheimer’s, dementia, endothelium, etiology, endothelial dysfunction, neurodegeneration, pathology, vascular

Address correspondence to: Dr. Roy L Soiza, c/o Dept of Medicine for The Elderly, Wards 303/304, Aberdeen Royal
Infirmary, Foresterhill, Aberdeen, AB25 2ZN, United Kingdom. Tel: 0044 1224 558109; E-mail:; Rory J
Kelleher, School of Medical Sciences, University of Aberdeen, United Kingdom. E-mail:
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