title: Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells.
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.
authors.affiliation: 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. DietrichH@nsurg.wustl.edu.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Dietrich
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Xiang
authors.forename: Byung H
authors.initials: BH
authors.lastname: Han
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Zipfel
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
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