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Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis

Insurmountable evidence has demonstrated a strong association between Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aβ) along cerebral vessel walls, impairs periv...

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Autores principales: Morrone, Christopher D., Bishay, Jossana, McLaurin, JoAnne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139584/
https://www.ncbi.nlm.nih.gov/pubmed/32183293
http://dx.doi.org/10.3390/ijms21061985
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author Morrone, Christopher D.
Bishay, Jossana
McLaurin, JoAnne
author_facet Morrone, Christopher D.
Bishay, Jossana
McLaurin, JoAnne
author_sort Morrone, Christopher D.
collection PubMed
description Insurmountable evidence has demonstrated a strong association between Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aβ) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD. To date, CAA research has been primarily focused on arterial Aβ, while the accumulation of Aβ in veins and venules were to a lesser extent. In this review, we describe preclinical models and clinical studies supporting the presence of venular amyloid and potential downstream pathological mechanisms that affect the cerebrovasculature in AD. Venous collagenosis, impaired cerebrovascular pulsatility, and enlarged perivascular spaces are exacerbated by venular amyloid and increase Aβ deposition, potentially through impaired perivascular clearance. Gaining a comprehensive understanding of the mechanisms involved in venular Aβ deposition and associated pathologies will give insight to how CAA contributes to AD and its association with AD-related cerebrovascular disease. Lastly, we suggest that special consideration should be made to develop Aβ-targeted therapeutics that remove vascular amyloid and address cerebrovascular dysfunction in AD.
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spelling pubmed-71395842020-04-10 Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis Morrone, Christopher D. Bishay, Jossana McLaurin, JoAnne Int J Mol Sci Review Insurmountable evidence has demonstrated a strong association between Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aβ) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD. To date, CAA research has been primarily focused on arterial Aβ, while the accumulation of Aβ in veins and venules were to a lesser extent. In this review, we describe preclinical models and clinical studies supporting the presence of venular amyloid and potential downstream pathological mechanisms that affect the cerebrovasculature in AD. Venous collagenosis, impaired cerebrovascular pulsatility, and enlarged perivascular spaces are exacerbated by venular amyloid and increase Aβ deposition, potentially through impaired perivascular clearance. Gaining a comprehensive understanding of the mechanisms involved in venular Aβ deposition and associated pathologies will give insight to how CAA contributes to AD and its association with AD-related cerebrovascular disease. Lastly, we suggest that special consideration should be made to develop Aβ-targeted therapeutics that remove vascular amyloid and address cerebrovascular dysfunction in AD. MDPI 2020-03-14 /pmc/articles/PMC7139584/ /pubmed/32183293 http://dx.doi.org/10.3390/ijms21061985 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Morrone, Christopher D.
Bishay, Jossana
McLaurin, JoAnne
Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title_full Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title_fullStr Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title_full_unstemmed Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title_short Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
title_sort potential role of venular amyloid in alzheimer’s disease pathogenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139584/
https://www.ncbi.nlm.nih.gov/pubmed/32183293
http://dx.doi.org/10.3390/ijms21061985
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