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

Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand
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J. Clin. Med. 2019, 8(5), 651; https://doi.org/10.3390/jcm8050651
Received: 31 March 2019 / Revised: 29 April 2019 / Accepted: 6 May 2019 / Published: 10 May 2019
(This article belongs to the Special Issue Ageing and Neurodegeneration in the Retina and Brain)
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Abstract

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. View Full-Text
Keywords: Alzheimer’s disease; vascular dysfunction; β-amyloid; APOE; blood-brain barrier; neurovascular unit Alzheimer’s disease; vascular dysfunction; β-amyloid; APOE; blood-brain barrier; neurovascular unit
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Govindpani, K.; McNamara, L.G.; Smith, N.R.; Vinnakota, C.; Waldvogel, H.J.; Faull, R.L.; Kwakowsky, A. Vascular Dysfunction in Alzheimer’s Disease: A Prelude to the Pathological Process or a Consequence of It? J. Clin. Med. 2019, 8, 651.

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