Cerebrovascular damage may initiate molecular events leading to neurodegeneration.
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Major genetic risk factors for AD are linked to brain vascular dysfunction.
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Vascular risk factors increase incidence of sporadic AD.
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Midlife lifestyle changes may protect the neurovasculature and prevent AD.
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Vasculoprotective therapies may delay the onset and progression of AD.
Abstract
Vascular insults can initiate a cascade of molecular events leading to neurodegeneration, cognitive impairment, and dementia. Here, we review the cellular and molecular mechanisms in cerebral blood vessels and the pathophysiological events leading to cerebral blood flow dysregulation and disruption of the neurovascular unit and the blood–brain barrier, which all may contribute to the onset and progression of dementia and Alzheimer's disease (AD). Particularly, we examine the link between neurovascular dysfunction and neurodegeneration including the effects of AD genetic risk factors on cerebrovascular functions and clearance of Alzheimer's amyloid-β peptide toxin, and the impact of vascular risk factors, environment, and lifestyle on cerebral blood vessels, which in turn may affect synaptic, neuronal, and cognitive functions. Finally, we examine potential experimental treatments for dementia and AD based on the neurovascular model, and discuss some critical questions to be addressed by future studies. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock
This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock