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The Role of Basement Membranes in Cerebral Amyloid Angiopathy

Dementia is a neuropsychiatric syndrome characterized by cognitive decline in multiple domains, often leading to functional impairment in activities of daily living, disability, and death. The most common causes of age-related progressive dementia include Alzheimer’s disease (AD) and vascular cognit...

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Autores principales: Howe, Matthew D., McCullough, Louise D., Urayama, Akihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732667/
https://www.ncbi.nlm.nih.gov/pubmed/33329053
http://dx.doi.org/10.3389/fphys.2020.601320
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author Howe, Matthew D.
McCullough, Louise D.
Urayama, Akihiko
author_facet Howe, Matthew D.
McCullough, Louise D.
Urayama, Akihiko
author_sort Howe, Matthew D.
collection PubMed
description Dementia is a neuropsychiatric syndrome characterized by cognitive decline in multiple domains, often leading to functional impairment in activities of daily living, disability, and death. The most common causes of age-related progressive dementia include Alzheimer’s disease (AD) and vascular cognitive impairment (VCI), however, mixed disease pathologies commonly occur, as epitomized by a type of small vessel pathology called cerebral amyloid angiopathy (CAA). In CAA patients, the small vessels of the brain become hardened and vulnerable to rupture, leading to impaired neurovascular coupling, multiple microhemorrhage, microinfarction, neurological emergencies, and cognitive decline across multiple functional domains. While the pathogenesis of CAA is not well understood, it has long been thought to be initiated in thickened basement membrane (BM) segments, which contain abnormal protein deposits and amyloid-β (Aβ). Recent advances in our understanding of CAA pathogenesis link BM remodeling to functional impairment of perivascular transport pathways that are key to removing Aβ from the brain. Dysregulation of this process may drive CAA pathogenesis and provides an important link between vascular risk factors and disease phenotype. The present review summarizes how the structure and composition of the BM allows for perivascular transport pathways to operate in the healthy brain, and then outlines multiple mechanisms by which specific dementia risk factors may promote dysfunction of perivascular transport pathways and increase Aβ deposition during CAA pathogenesis. A better understanding of how BM remodeling alters perivascular transport could lead to novel diagnostic and therapeutic strategies for CAA patients.
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spelling pubmed-77326672020-12-15 The Role of Basement Membranes in Cerebral Amyloid Angiopathy Howe, Matthew D. McCullough, Louise D. Urayama, Akihiko Front Physiol Physiology Dementia is a neuropsychiatric syndrome characterized by cognitive decline in multiple domains, often leading to functional impairment in activities of daily living, disability, and death. The most common causes of age-related progressive dementia include Alzheimer’s disease (AD) and vascular cognitive impairment (VCI), however, mixed disease pathologies commonly occur, as epitomized by a type of small vessel pathology called cerebral amyloid angiopathy (CAA). In CAA patients, the small vessels of the brain become hardened and vulnerable to rupture, leading to impaired neurovascular coupling, multiple microhemorrhage, microinfarction, neurological emergencies, and cognitive decline across multiple functional domains. While the pathogenesis of CAA is not well understood, it has long been thought to be initiated in thickened basement membrane (BM) segments, which contain abnormal protein deposits and amyloid-β (Aβ). Recent advances in our understanding of CAA pathogenesis link BM remodeling to functional impairment of perivascular transport pathways that are key to removing Aβ from the brain. Dysregulation of this process may drive CAA pathogenesis and provides an important link between vascular risk factors and disease phenotype. The present review summarizes how the structure and composition of the BM allows for perivascular transport pathways to operate in the healthy brain, and then outlines multiple mechanisms by which specific dementia risk factors may promote dysfunction of perivascular transport pathways and increase Aβ deposition during CAA pathogenesis. A better understanding of how BM remodeling alters perivascular transport could lead to novel diagnostic and therapeutic strategies for CAA patients. Frontiers Media S.A. 2020-11-25 /pmc/articles/PMC7732667/ /pubmed/33329053 http://dx.doi.org/10.3389/fphys.2020.601320 Text en Copyright © 2020 Howe, McCullough and Urayama. 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 or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) 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 Physiology
Howe, Matthew D.
McCullough, Louise D.
Urayama, Akihiko
The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title_full The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title_fullStr The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title_full_unstemmed The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title_short The Role of Basement Membranes in Cerebral Amyloid Angiopathy
title_sort role of basement membranes in cerebral amyloid angiopathy
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732667/
https://www.ncbi.nlm.nih.gov/pubmed/33329053
http://dx.doi.org/10.3389/fphys.2020.601320
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