Title

Cerebrovascular and Blood-Brain Barrier Compromise: A Mechanistic Link between Vascular Disease and Alzheimer’s Disease Subtypes of Neurocognitive Disorders

Document Type

Article

Version Deposited

None (link only)

Publication Date

10-12-2015

Publication Title

Journal of Parkinson's disease and Alzheimer’s disease

DOI

10.13188/2376-922X.1000013

Abstract

Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common subtypes of neurocognitive disorders (NCDs), with overlapping clinical presentation and risk factors. Studies on AD brains have demonstrated increased extravasation of plasma components through a functionally compromised blood-brain barrier (BBB). The BBB includes endothelial cells, astrocyte foot processes, basement membrane, and pericytes, and its function is to maintain brain homeostasis by limiting entry of plasma components into the brain. The pathogenesis of VaD is commonly attributed to cerebrovascular lesions, and neuroimaging studies have demonstrated extravasation of plasma components. Although the pathogenesis of AD and VaD is unknown, much evidence suggests that an abnormal cerebrovasculature may be a common mechanistic link. The primary aims of this review are to highlight studies that embrace or oppose this theory, and to examine the potentially causal relationship between cerebrovascular abnormalities and pathological hallmarks of AD. A major challenge to elucidate the role of the BBB in AD pathology has been the inability to demonstrate BBB dysfunction in neuroimaging studies. Computed tomography and magnetic resonance imaging can detect leakage from larger vessels, significant for VaD, but fail to detect smaller chronic vascular leakages common to AD. The latter are, however, detected by routine immunohistological techniques in postmortem tissues. If we consider AD and VaD from the vascular perspective, they have many features in common. By placing these diseases along a continuum of vascular pathology manifesting as dementia, it becomes apparent that the observed clinical differences are mostly attributable to the extent and location of the vascular leak. Lastly, we propose a novel hypothesis that we believe can potentially account for much of the phenomenology surrounding AD and its pathogenesis, including mechanisms of intraneuronal amyloid deposition and amyloid plaque formation, and the role of the BBB and autoantibodies in this process.

Comments

Copyright: © 2015 Goldwaser EL, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Parkinson’s Disease and Alzheimer’s Disease is an international online Open Access peer reviewed journal that encompasses all areas of basic, translational, and clinical research to treat, delay, or prevent these devastating diseases.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Published Citation

Goldwaser EL, Acharya NK, Nagele RG. Cerebrovascular and Blood-Brain Barrier Compromise: A Mechanistic Link between Vascular Disease and Alzheimer’s Disease Subtypes of Neurocognitive Disorders. J Parkinsons Dis Alzheimer Dis. 2015;2(2): 10.

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