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• APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.
• Citation:
  Irizarry M, McNamara M, Fedorchak K, Hsiao K, Hyman B
  

  APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.

  Journal of neuropathology and experimental neurology. 1997 Sep;56(9):965-73
  [PubMed] [Alzforum]
• Supporting:
  • Mouse models overexpressing mutant human APP have reproduced overproduction of Aβ peptides and progressive amyloid deposition, but they have largely failed to reproduce neurodegeneration.

    SHOW Details   Supporting(1)   Consistent(3)   Inconsistent(2)   Alternative to: (2)    Genes/Proteins: (1)

    Experimental Approach: Pathophysiology,   Genetics,   Animal models,   Mechanism - biochemistry and structural biology
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Irizarry M, McNamara M, Fedorchak K, Hsiao K, Hyman B
      APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.
      Journal of neuropathology and experimental neurology. 1997 Sep;56(9):965-73

    Consistent statements
    

    • Relevant Aβ toxicity has barely been demonstrated, and none of the data amounts to convincing support that Aβ toxicity causes massive cell loss seen in Alzheimer Disease. Hardy  
    • Transgenic mice that demonstrate progressive Aβ deposition often do not suffer neuronal loss. Hardy J  Selkoe D 
    • Aβ deposition has not been found to be toxic or cause damage and death of nerve cells in human or animal brain. Aliev G 

    Inconsistent statements
    

    • Increasing intraneuronal Aβ42 leads to an age-dependent neuron loss in hippocampus in two different APP/PS1 transgenic mouse models with no correlation to extracellular Aβ. Bayer T 
    • Aβ peptides are neurotoxic and key to neurodegeneration in AD. Plant L  Webster N  Boyle J  Ramsden M  Freir D  Peers C  Pearson H 

    Alternative statements
    

    • Aβ has been shown to exacerbate neurodegeneration in cultured neurons when glucose levels are reduced. Cotman C  Su J 
    • APP V717F and APPSw transgenic mice develop neuritic plaque in the presence of mouse ApoE, but no neuritic dystrophy developed in the absence of ApoE. Holtzman D 

    Genes/Proteins
    

    • Protein: Amyloid beta A4 protein [Homo sapiens]
  • Transgenic mice that demonstrate progressive Aβ deposition often do not suffer neuronal loss.

    SHOW Details   Supporting(4)   Consistent(1)   Alternative to: (2)

    Experimental Approach: Pathophysiology,   Mechanism - molecular and cell,   Animal models,  
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G
      Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.
      Science (New York, N.Y.). 1996 Oct 4;274(5284):99-102
    • Irizarry M, McNamara M, Fedorchak K, Hsiao K, Hyman B
      APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.
      Journal of neuropathology and experimental neurology. 1997 Sep;56(9):965-73
    • Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F
      Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.
      Nature. 1995 Feb 9;373(6514):523-7
    • Irizarry M, Soriano F, McNamara M, Page K, Schenk D, Games D, Hyman B
      Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 1997 Sep 15;17(18):7053-9

    Consistent statements
    

    • Mouse models overexpressing mutant human APP have reproduced overproduction of Aβ peptides and progressive amyloid deposition, but they have largely failed to reproduce neurodegeneration. Shen J  Kelleher R 

    Alternative statements
    

    • Young APP transgenic mice undergo synaptic, electrophysiological and behavioral changes before amyloid plaque deposition. Walsh D  Klyubin I  Fadeeva J  Cullen W  Anwyl R  Wolfe M  Rowan M  Selkoe D 
    • Transgenic mice demonstrate neurologic deficits prior to appearance of amyloid deposits. Bitan G  Kirkitadze M  Lomakin A  Vollers S  Benedek G  Teplow D 
  • Tg2576 mice are a good model to study pre-clinical stages of Alzheimer Disease.

    SHOW Details   Supporting(3) 

    Description: Tg2576 mice exhibit an early decline in spatial reference memory at 6 months of age which remains stable for the following 7-8 months. This stage of earliest memory function decline precedes neuropathology.
    Experimental Approach: Animal models,   Genetics,   Pathophysiology
    Pathogenic Narrative Tags: Perturbation
    Supporting Evidence
    

    • Irizarry M, McNamara M, Fedorchak K, Hsiao K, Hyman B
      APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1.
      Journal of neuropathology and experimental neurology. 1997 Sep;56(9):965-73
    • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G
      Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.
      Science (New York, N.Y.). 1996 Oct 4;274(5284):99-102
    • Benzing W, Wujek J, Ward E, Shaffer D, Ashe K, Younkin S, Brunden K
      Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice.
      Neurobiology of aging. 1999;20(6):581-9
• Created On: Wed, Apr 23 07:53:35 EDT 2008
• Last Modified On: Wed Apr 23 07:53:35 EDT 2008