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• Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
• Citation:
  Fryer J, Taylor J, DeMattos R, Bales K, Paul S, Parsadanian M, Holtzman D
  

  Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Aug 27;23(21):7889-96
  [PubMed] [Alzforum]
• Supporting:
  • In the absence of endogenous murine apoE, APPsw mice still develop Aβ deposits, but the vast majority of the plaques are nonfibrillar, and the formation of CAA and CAA-associated hemorrhage is completely absent even at very old ages.

    SHOW Details   Supporting(2)     Genes/Proteins: (5)

    Experimental Approach: Genetics,   Pathophysiology,   Animal models
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Fryer J, Taylor J, DeMattos R, Bales K, Paul S, Parsadanian M, Holtzman D
      Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Aug 27;23(21):7889-96
    • Holtzman D, Fagan A, Mackey B, Tenkova T, Sartorius L, Paul S, Bales K, Ashe K, Irizarry M, Hyman B
      Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model.
      Annals of neurology. 2000 Jun;47(6):739-47

    Genes/Proteins
    

    • Gene: APP amyloid beta (A4) precursor protein [Homo sapiens]
    • Gene: APOE apolipoprotein E [Homo sapiens]
    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
    • Protein: Amyloid beta A4 protein [Homo sapiens]
  • Further evidence from transgenic mouse studies demonstrate the effects of ApoE on the development of cerebral amyloid angiopathy.

    SHOW Details   Supporting(2)   Consistent(1) 

    Experimental Approach: Genetics,   Animal models,   Pathophysiology
    Pathogenic Narrative Tags: Pathologic change
    Supporting Evidence
    

    • Fryer J, Taylor J, DeMattos R, Bales K, Paul S, Parsadanian M, Holtzman D
      Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Aug 27;23(21):7889-96
    • Fryer J, Simmons K, Parsadanian M, Bales K, Paul S, Sullivan P, Holtzman D
      Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005 Mar 16;25(11):2803-10

    Consistent statements
    

    • In vivo studies with transgenic mouse models of AD demonstrate the effects of ApoE on AD and CAA-related neuropathology. Holtzman D 
  • ApoE has been shown to be critically important for the formation of fibrillar Aβ in brain parenchyma and CAA in vivo.

    SHOW Details   Supporting(2)   Consistent(5)     Genes/Proteins: (3)

    Experimental Approach: Pathophysiology
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Fryer J, Taylor J, DeMattos R, Bales K, Paul S, Parsadanian M, Holtzman D
      Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Aug 27;23(21):7889-96
    • Holtzman D, Fagan A, Mackey B, Tenkova T, Sartorius L, Paul S, Bales K, Ashe K, Irizarry M, Hyman B
      Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model.
      Annals of neurology. 2000 Jun;47(6):739-47

    Consistent statements
    

    • CAA is a frequent cause of CNS hemorrhage and stroke in the elderly. Holtzman D 
    • ApoE2 allele is linked to greater risk of CAA-associated vasculopathy and CNS hemorrhage. Holtzman D 
    • ApoE4 alleles, which increase risk of AD, also increase Aβ accumulation. Lambert M  Barlow A  Chromy B  Edwards C  Freed R  Liosatos M  Morgan T  Rozovsky I  Trommer B  Viola K  Wals P  Zhang C  Finch C  Krafft G  Klein W 
    • ApoE plays a critical and isoform specific role in conversion of Aβ to a fibrillar form with ensuing neuritic-plaque formation, a key pathological hallmark of AD. Holtzman D 
    • ApoE is critical for the neuritic dystrophy (neuritic plaques) of AD because it is associated with fibrillar amyloid formation. Holtzman D 

    Genes/Proteins
    

    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
    • Protein: Apolipoprotein E [Homo sapiens]
  • An additional study supports the claim that APPsw but not APPV717F develop CAA.

    SHOW Details   Supporting(1)   Consistent(1) 

    Experimental Approach: Animal models,   Genetics,   Pathophysiology
    Pathogenic Narrative Tags: Perturbation
    Supporting Evidence
    

    • Fryer J, Taylor J, DeMattos R, Bales K, Paul S, Parsadanian M, Holtzman D
      Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2003 Aug 27;23(21):7889-96

    Consistent statements
    

    • APPSw but not APPV717F develop prominent CAA. Holtzman D 
• Created On: Wed, Apr 23 04:14:05 EDT 2008
• Last Modified On: Wed Apr 23 04:14:05 EDT 2008