title: Cerebral amyloid angiopathy increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice.
abstract: OBJECTIVE
  We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown.
  
  
  METHODS
  To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls).
  
  
  RESULTS
  We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion.
  
  
  CONCLUSIONS
  These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury.
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Eric
authors.initials: E
authors.lastname: Milner
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Johnson
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Ananth K
authors.initials: AK
authors.lastname: Vellimana
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Greenberg
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Byung Hee
authors.initials: BH
authors.lastname: Han
authors.affiliation: From the Department of Neurological Surgery (E.M., M.-L.Z., A.W.J., A.K.V., J.K.G., B.H.H., G.J.Z.), Program in Neuroscience (E.M.), Department of Neurology (D.M.H., G.J.Z.), Department of Developmental Biology (D.M.H.), and Hope Center for Neurological Disorders (D.M.H., B.H.H., G.J.Z.), Washington University School of Medicine, St. Louis, MO. zipfelg@wustl.edu.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Zipfel
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology*; D004198:Disease Susceptibility; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
keywords: Alzheimer disease; amyloid angiopathy; amyloid β-peptide; brain ischemia; mice, transgenic