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Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease

Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact...

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Detalles Bibliográficos
Autores principales: Gupta, Ajay, Iadecola, Costantino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468824/
https://www.ncbi.nlm.nih.gov/pubmed/26136682
http://dx.doi.org/10.3389/fnagi.2015.00115
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author Gupta, Ajay
Iadecola, Costantino
author_facet Gupta, Ajay
Iadecola, Costantino
author_sort Gupta, Ajay
collection PubMed
description Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of amyloid-β peptide (Aβ), a peptide central to AD pathology, Aβ, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of Aβ is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing Aβ clearance and elevating brain levels of Aβ. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with Aβ clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition.
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spelling pubmed-44688242015-07-01 Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease Gupta, Ajay Iadecola, Costantino Front Aging Neurosci Neuroscience Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of amyloid-β peptide (Aβ), a peptide central to AD pathology, Aβ, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of Aβ is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing Aβ clearance and elevating brain levels of Aβ. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with Aβ clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition. Frontiers Media S.A. 2015-06-16 /pmc/articles/PMC4468824/ /pubmed/26136682 http://dx.doi.org/10.3389/fnagi.2015.00115 Text en Copyright © 2015 Gupta and Iadecola. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Gupta, Ajay
Iadecola, Costantino
Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title_full Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title_fullStr Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title_full_unstemmed Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title_short Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer’s disease
title_sort impaired aβ clearance: a potential link between atherosclerosis and alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468824/
https://www.ncbi.nlm.nih.gov/pubmed/26136682
http://dx.doi.org/10.3389/fnagi.2015.00115
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