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Cell Mol Neurobiol. 2016 Mar;36(2):155-65. doi: 10.1007/s10571-015-0256-9. Epub 2015 Sep 2.

Endothelial Dysfunction and Amyloid-β-Induced Neurovascular Alterations.

Author information

1
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street; RR-410, New York, NY, 10065, USA.
2
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street; RR-410, New York, NY, 10065, USA. lap2003@med.cornell.edu.

Abstract

Alzheimer's disease (AD) and cerebrovascular diseases share common vascular risk factors that have disastrous effects on cerebrovascular regulation. Endothelial cells, lining inner walls of cerebral blood vessels, form a dynamic interface between the blood and the brain and are critical for the maintenance of neurovascular homeostasis. Accordingly, injury in endothelial cells is regarded as one of the earliest symptoms of impaired vasoregulatory mechanisms. Extracellular buildup of amyloid-β (Aβ) is a central pathogenic factor in AD. Aβ exerts potent detrimental effects on cerebral blood vessels and impairs endothelial structure and function. Recent evidence implicates vascular oxidative stress and activation of the non-selective cationic channel transient receptor potential melastatin (TRPM)-2 on endothelial cells in the mechanisms of Aβ-induced neurovascular dysfunction. Thus, Aβ triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca(2+) overload and vasomotor dysfunction. The cerebrovascular dysfunction may contribute to AD pathogenesis by reducing the cerebral blood supply, leading to increased susceptibility to vascular insufficiency, and by promoting Aβ accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease.

KEYWORDS:

Alzheimer’s disease; Cerebral blood flow; Cerebral endothelial cells; TRPM2; β-amyloid

PMID:
26328781
PMCID:
PMC4775455
[Available on 2017-03-01]
DOI:
10.1007/s10571-015-0256-9
[Indexed for MEDLINE]
Free PMC Article

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