AlzSWAN Knowledge Base

Powered by SWAN (Semantic Web Applications in Neuromedicine)

• Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?
• Citation:
  Jarrett J, Lansbury P
  

  Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?

  Cell. 1993 Jun 18;73(6):1055-8
  [PubMed] [Alzforum]
• Supporting:
  • Amyloid increases through Aβ concentration-dependent seeded polymerization.

    SHOW Details   Supporting(1)   Consistent(2)     Genes/Proteins: (2)

    Experimental Approach: Mechanism - biochemistry and structural biology,  
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Jarrett J, Lansbury P
      Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?
      Cell. 1993 Jun 18;73(6):1055-8

    Consistent statements
    

    • The polymerization of soluble Aβ, which leads to plaque formation, is nucleated by “seeds” of oligomeric Aβ, but it remains unclear where seeds of polymerized Aβ originate or how they are formed. Muresan Z  Muresan V 
    • Conversion of Aβ from a soluble form to fibrillar form occurs via “seeded” polymerization of Aβ40 and Aβ42. Holtzman D 

    Genes/Proteins
    

    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
  • I disagree with the suggestion that the appearance of a plaque within a day or two does not fit in with data on nucleation-dependent polymerization

    SHOW Details   Supporting(1)   Inconsistent(2) 

    Experimental Approach: Mechanism - biochemistry and structural biology
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Jarrett J, Lansbury P
      Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?
      Cell. 1993 Jun 18;73(6):1055-8

    Inconsistent statements
    

    • It has been generally accepted, based on in vitro studies of protein aggregation, that amyloid-beta aggregation is time dependent and follows a relatively slow nucleation-dependent polymerization process. 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 
    • Senile plaque formation is a very rapid event, with five new plaques appearing precipitously within 24 h after the last imaging session. 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 
  • It has been generally accepted, based on in vitro studies of protein aggregation, that amyloid-beta aggregation is time dependent and follows a relatively slow nucleation-dependent polymerization process.

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

    Experimental Approach: Mechanism - biochemistry and structural biology,  
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Jarrett J, Lansbury P
      Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?
      Cell. 1993 Jun 18;73(6):1055-8

    Consistent statements
    

    • The quick growth of dense plaques suggests that dense plaques grow not only with Aβ monomer addition, but perhaps also by capturing oligomeric intermediates at the fiber ends, as shown earlier for prion proteins (Serio et al., 2000; Collins et al., 2004). Kumar-Singh S 
    • In a simple model of Aβ42 assembly, monomers quickly assemble to form pentamer/hexamer units, "paranuclei" which have little regular secondary structure and which in turn aggregate to form larger oligomers of paranuclei, leading to the formation into protofibrils. Bitan G  Kirkitadze M  Lomakin A  Vollers S  Benedek G  Teplow D 

    Inconsistent statements
    

    • The rate of growth measured in this study is exactly what the nucleation model would predict and it is gratifying to see this occur in vivo. Lansbury P 
    • I disagree with the suggestion that the appearance of a plaque within a day or two does not fit in with data on nucleation-dependent polymerization Lansbury P 

    Alternative statements
    

    • Live multiphoton imaging cannot yet visualize the prior accumulation of Aβ or the nucleation event. Lansbury P 
• Created On: Wed, Apr 23 08:01:58 EDT 2008
• Last Modified On: Wed Apr 23 08:01:58 EDT 2008