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Mol Neurodegener. 2010 Apr 13;5:15. doi: 10.1186/1750-1326-5-15.

Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells.

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Department of Neurological Surgery, Hope Center for Neurological Disorders, and Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, 63110, USA.



Evidence indicates that soluble forms of amyloid-beta (Abeta) are vasoactive, which may contribute to cerebrovascular dysfunction noted in patients with Alzheimer's Disease and cerebral amyloid angiopathy. The effects of soluble Abeta on penetrating cerebral arterioles - the vessels most responsible for controlling cerebrovascular resistance - have not been studied.


Freshly dissolved Abeta1-40 and Abeta1-42, but not the reverse peptide Abeta40-1 constricted isolated rat penetrating arterioles and diminished dilation to adenosine tri-phosphate (ATP). Abeta1-42 also enhanced ATP-induced vessel constriction. Abeta1-40 diminished arteriolar myogenic response, and an anti-Abeta antibody reduced Abeta1-40 induced arteriolar constriction. Prolonged Abeta exposure in vessels of Tg2576 mice resulted in a marked age-dependent effect on ATP-induced vascular responses. Vessels from 6 month old Tg2576 mice had reduced vascular responses whereas these were absent from 12 month old animals. Abeta1-40 and Abeta1-42 acutely increased production of reactive oxygen species (ROS) in cultured rat cerebro-microvascular cells. The radical scavenger MnTBAP attenuated this Abeta-induced oxidative stress and Abeta1-40-induced constriction in rat arterioles.


Our results suggest that soluble Abeta1-40 and Abeta1-42 directly affect the vasomotor regulation of isolated rodent penetrating arterioles, and that ROS partially mediate these effects. Once insoluble Abeta deposits are present, arteriolar reactivity is greatly diminished.

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