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

Dietrich HH, Xiang C, Han BH, Zipfel GJ, Holtzman DM (2010). Mol Neurodegener, 5:15. PMID:20388225 Read More

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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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Posted on October 7, 2010
Posted in: HPAN, Neurodegeneration, Neurogenetics, Neurovascular Injury & Repair, Publications Authors: , , ,