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Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?

Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there...

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Autores principales: Govindpani, Karan, McNamara, Laura G, Smith, Nicholas R, Vinnakota, Chitra, Waldvogel, Henry J, Faull, Richard LM, Kwakowsky, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571853/
https://www.ncbi.nlm.nih.gov/pubmed/31083442
http://dx.doi.org/10.3390/jcm8050651
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author Govindpani, Karan
McNamara, Laura G
Smith, Nicholas R
Vinnakota, Chitra
Waldvogel, Henry J
Faull, Richard LM
Kwakowsky, Andrea
author_facet Govindpani, Karan
McNamara, Laura G
Smith, Nicholas R
Vinnakota, Chitra
Waldvogel, Henry J
Faull, Richard LM
Kwakowsky, Andrea
author_sort Govindpani, Karan
collection PubMed
description Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition, neurotoxicity, glial activation and metabolic dysfunction in multiple cell types. A vicious feedback cycle ensues, with progressively worsening neuronal and vascular pathology through the course of the disease. Thus, a better appreciation for the importance of vascular dysfunction in AD may open new avenues for research and therapy.
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spelling pubmed-65718532019-06-18 Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It? Govindpani, Karan McNamara, Laura G Smith, Nicholas R Vinnakota, Chitra Waldvogel, Henry J Faull, Richard LM Kwakowsky, Andrea J Clin Med Review Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition, neurotoxicity, glial activation and metabolic dysfunction in multiple cell types. A vicious feedback cycle ensues, with progressively worsening neuronal and vascular pathology through the course of the disease. Thus, a better appreciation for the importance of vascular dysfunction in AD may open new avenues for research and therapy. MDPI 2019-05-10 /pmc/articles/PMC6571853/ /pubmed/31083442 http://dx.doi.org/10.3390/jcm8050651 Text en © 2019 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
Govindpani, Karan
McNamara, Laura G
Smith, Nicholas R
Vinnakota, Chitra
Waldvogel, Henry J
Faull, Richard LM
Kwakowsky, Andrea
Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title_full Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title_fullStr Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title_full_unstemmed Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title_short Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It?
title_sort vascular dysfunction in alzheimer’s disease: a prelude to the pathological process or a consequence of it?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571853/
https://www.ncbi.nlm.nih.gov/pubmed/31083442
http://dx.doi.org/10.3390/jcm8050651
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