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• Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease.
• Citation:
  Knowles R, Wyart C, Buldyrev S, Cruz L, Urbanc B, Hasselmo M, Stanley H, Hyman B
  

  Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease.

  Proceedings of the National Academy of Sciences of the United States of America. 1999 Apr 27;96(9):5274-9
  [PubMed] [Alzforum]
• Supporting:
  • Imaging of neurite dystrophy and new plaque formation over time demonstrated that in the days after plaque formation, progressive neuritic alterations were evident: from a smooth bend around the new plaque to very tortuous changes identical in appearance to dystrophic neurites seen in Alzheimer’s disease

    SHOW Details   Supporting(2)   Consistent(3)   Inconsistent(2) 

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

    • Knowles R, Wyart C, Buldyrev S, Cruz L, Urbanc B, Hasselmo M, Stanley H, Hyman B
      Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease.
      Proceedings of the National Academy of Sciences of the United States of America. 1999 Apr 27;96(9):5274-9
    • Meyer-Luehmann M, Spires-Jones T, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman D, Bacskai B, Hyman B
      Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease.
      Nature. 2008 Feb 7;451(7179):720-4

    Consistent statements
    

    • In parallel with characteristic AD pathology, Aβ induces the formation of dystrophic neurites in cultured neurons. Cotman C  Su J 
    • Aβ induces local neurite degeneration referred to as neuritic apoptosis or synaptotosis which displays the morphological and biochemical characteristics of apoptosis. Thus neurite degeneration may use mechanisms common to apoptotsis. Cotman C 
    • Accumulation of Aβ begins within neurites, prior to any major signs of neurodegeneration or cell death, although the terminals that contain accumulations appear dystrophic. Muresan Z  Muresan V 

    Inconsistent statements
    

    • FAD APP mutations cause axonal trafficking defects and that that, in turn, stimulates the proteolytic processing of APP and generation of Aβ Kumar-Singh S 
    • The development of dystrophic neurites in APP transgenic mice precedes plaques by more than a year. Kumar-Singh S 
  • Quantitative analysis of neurite curvature showed that in the immediate vicinity of plaques the tortuosity increased gradually over the first week, and is indistinguishable from neuritic curvature observed at time of death. This suggests that the neuritic changes that occur immediately in response to plaque is essentially to a maximal extent.

    SHOW Details   Supporting(3)   Inconsistent(1)   Alternative to: (1)

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

    • Le R, Cruz L, Urbanc B, Knowles R, Hsiao-Ashe K, Duff K, Irizarry M, Stanley H, Hyman B
      Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruption.
      Journal of neuropathology and experimental neurology. 2001 Aug;60(8):753-8
    • Knowles R, Wyart C, Buldyrev S, Cruz L, Urbanc B, Hasselmo M, Stanley H, Hyman B
      Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease.
      Proceedings of the National Academy of Sciences of the United States of America. 1999 Apr 27;96(9):5274-9
    • Meyer-Luehmann M, Spires-Jones T, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman D, Bacskai B, Hyman B
      Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease.
      Nature. 2008 Feb 7;451(7179):720-4

    Inconsistent statements
    

    • There are a number of previous studies (cited in Stokin et al., 2005) that find significant axonal dystrophies, which may be indicative of defects in axonal transport, prior to amyloid deposition as well as in regions of the brain that lack amyloid deposition. Goldstein L 

    Alternative statements
    

    • The experiments of Meyer-Luehmann et al. primarily focus on cortical regions, while many of the experiments in Stokin et al. examined basal forebrain cholinergic axons, which are long projection axons in regions distinct from the cortical regions imaged in the present paper. Goldstein L 
• Created On: Wed, Apr 23 04:50:50 EDT 2008
• Last Modified On: Wed Apr 23 04:50:50 EDT 2008