947460
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947784
stoichiometry: 1.0
species: 947436
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947508
constant: true
value: 2.1E-5
type: Parameter

947700
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species: 947484
type: SpeciesReference

947988
stoichiometry: 1.0
species: 947484
type: SpeciesReference

947880
stoichiometry: 1.0
species: 947424
type: SpeciesReference

947940
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species: 947448
type: SpeciesReference

947616
stoichiometry: 1.0
species: 947460
type: SpeciesReference

947556
constant: true
value: 2.785E-6
type: Parameter

947484
is version of: P08473
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 1000.0
in compartment: 947412
name: Neprilysin
type: Species

947868
modifier: 309568
reversible: false
reactant: 947880
product: 947904
modifier: 309580
kinetic law: 947916
reactant: 947892
fast: false
type: Reaction

947532
constant: true
value: 8.4655E-6
type: Parameter

947664
stoichiometry: 1.0
species: 947424
type: SpeciesReference

947448
is version of: CHEBI:64645
name: AbetaPlaque
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is version of: BTO:0002774
type: Species
initial amount: 0.0
initial concentration: NaN
boundary condition: false
has only substance units: true
in compartment: 947412

947748
stoichiometry: 1.0
species: 947436
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947844
stoichiometry: 4.0
species: 947448
type: SpeciesReference

948000
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species: 947472
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947820
kinetic law: 947856
modifier: 309556
product: 947844
reactant: 947832
fast: false
reversible: false
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947424
is version of: CHEBI:64645
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
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name: AbetaMonomer
type: Species

947412
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

947724
kinetic law: 947760
modifier: 309532
product: 947748
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fast: false
reversible: false
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947472
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947772
kinetic law: 947808
modifier: 309544
product: 947796
reactant: 947784
fast: false
reversible: false
type: Reaction

947520
constant: true
value: 1.1783E-7
type: Parameter

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modifier: 309496
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reactant: 947616
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947796
stoichiometry: 2.0
species: 947424
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constant: true
value: 1.86E-5
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947580
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value: 4.0
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value: 5.4357E-5
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947892
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species: 947448
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947628
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species: 947424
type: SpeciesReference

947568
constant: true
value: 0.00574
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947832
stoichiometry: 2.0
species: 947436
type: SpeciesReference

947952
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species: 947424
type: SpeciesReference

947592
constant: true
value: 1.8E-10
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947400
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
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name: AbetaDimer
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type: Species
has only substance units: true
is version of: CHEBI:64645
initial amount: 0.0
boundary condition: false
constant: false
is version of: GO:0043234
initial concentration: NaN

947736
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species: 947424
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947688
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species: 947472
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modifier: 309604
product: 948000
reactant: 947988
fast: false
reversible: false
type: Reaction

BIOMD0000000462
units def: 947388
reaction: 947820
parameter: 947592
parameter: 947520
substance units: 947388
creator:
  ORG:
    orgname: University of Newcastle
  n:
    given: Carole
    family: Proctor
created:
  W3 CDTF: Thu Jun 06 20:51:15 BST 2013
reaction: 947604
species: 947424
parameter: 947580
parameter: 947544
species: 947436
parameter: 947532
reaction: 947868
reaction: 947928
species: 947448
occurs in: http://identifiers.org/taxonomy/9606
length unit: length
type: SBMLModel
reaction: 947772
curated: true
reaction: 947976
reaction: 947724
species: 947460
species: 947472
species: 947484
reaction: 947652
parameter: 947568
parameter: 947496
parameter: 947556
is described by: http://identifiers.org/pubmed/22748062
is version of: GO:0097242
name: Proctor2012 - Amyloid-beta aggregation
area units: area
is version of: GO:0070841
parameter: 947508
compartment: 947412
notes: Proctor2012 - Amyloid-beta aggregation This model supports the current thinking that levels of dimers are important in initiating the aggregation process. This model is described in the article: Aggregation, impaired degradation and immunization targeting of amyloid-beta dimers in Alzheimer's disease: a stochastic modelling approach. Proctor CJ, Pienaar IS, Elson JL, Kirkwood TB Molecular Neurodegeneration. 2012; 7:32 Abstract: BACKGROUND: Alzheimer's disease (AD) is the most frequently diagnosed neurodegenerative disorder affecting humans, with advanced age being the most prominent risk factor for developing AD. Despite intense research efforts aimed at elucidating the precise molecular underpinnings of AD, a definitive answer is still lacking. In recent years, consensus has grown that dimerisation of the polypeptide amyloid-beta (Aß), particularly Aß₄₂, plays a crucial role in the neuropathology that characterise AD-affected post-mortem brains, including the large-scale accumulation of fibrils, also referred to as senile plaques. This has led to the realistic hope that targeting Aß₄₂ immunotherapeutically could drastically reduce plaque burden in the ageing brain, thus delaying AD onset or symptom progression. Stochastic modelling is a useful tool for increasing understanding of the processes underlying complex systems-affecting disorders such as AD, providing a rapid and inexpensive strategy for testing putative new therapies. In light of the tool's utility, we developed computer simulation models to examine Aß₄₂ turnover and its aggregation in detail and to test the effect of immunization against Aß dimers. RESULTS: Our model demonstrates for the first time that even a slight decrease in the clearance rate of Aß₄₂ monomers is sufficient to increase the chance of dimers forming, which could act as instigators of protofibril and fibril formation, resulting in increased plaque levels. As the process is slow and levels of Aβ are normally low, stochastic effects are …
modified:
  W3 CDTF: Mon Jun 10 14:04:43 BST 2013
is: MODEL1202290000
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah

947652
reactant: 947676
product: 947700
product: 947688
reversible: false
type: Reaction
kinetic law: 947712
fast: false
modifier: 309508
reactant: 947664
modifier: 309520