Journal
CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 36, Issue 2, Pages 155-165Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-015-0256-9
Keywords
Alzheimer's disease; beta-amyloid; Cerebral blood flow; Cerebral endothelial cells; TRPM2
Categories
Funding
- National Institutes of Health [NS37853]
- American Heart Association [09SDG2060701]
- Feil Family Foundation
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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-beta (A beta) is a central pathogenic factor in AD. A beta 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 A beta-induced neurovascular dysfunction. Thus, A beta triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca2+ 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 A beta accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease.
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