title: Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease.
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.
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Sweeney
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Abhay P
authors.initials: AP
authors.lastname: Sagare
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA. Electronic address: zlokovic@usc.edu.
authors.forename: Berislav V
authors.initials: BV
authors.lastname: Zlokovic
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003704:Dementia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D000069336:Neurovascular Coupling; D012307:Risk Factors
keywords: Alzheimer's disease; Blood–brain barrier; Dementia; Neurovascular medicine; Neurovascular unit; Vascular factors