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

Rory J. Kelleher, Roy L Soiza

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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.

Original languageEnglish
Pages (from-to)197-226
Number of pages30
JournalAmerican Journal of Cardiovascular Disease
Issue number4
Early online date1 Nov 2013
Publication statusPublished - 15 Nov 2013

Bibliographical note

Dr Soiza is funded by an NRS Career Research Fellowship. The authors are grateful to Alzheimer’s Research UK for providing funding.


  • Journal Article
  • Review
  • Alzheimer’s
  • dementia
  • etiology
  • endothelial dysfunction
  • neurodegeneration
  • pathology
  • vascular disease


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