Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (deterministic version)

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Short description
Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (deterministic version)

Extension of a previously published stochastic model (designed to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau ( BIOMD0000000286, BIOMD0000000462)) to include the main processes involved in passive and active immunisation against Aβ and then to demonstrate the effects of this intervention on soluble Aβ. This is the deterministic version of the model, the stochastic version is BIOMD0000000634.

This model is described in the article:

Proctor CJ, Boche D, Gray DA, Nicoll JA.
PLoS ONE 2013; 8(9): e73631

Abstract:

Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Investigating interventions in Alzheimer's disease with computer simulation models.
  • Proctor CJ, Boche D, Gray DA, Nicoll JA
  • PloS one , 0/ 2013 , Volume 8 , pages: e73631
  • Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Progress in the development of therapeutic interventions to treat or slow the progression of Alzheimer's disease has been hampered by lack of efficacy and unforeseen side effects in human clinical trials. This setback highlights the need for new approaches for pre-clinical testing of possible interventions. Systems modelling is becoming increasingly recognised as a valuable tool for investigating molecular and cellular mechanisms involved in ageing and age-related diseases. However, there is still a lack of awareness of modelling approaches in many areas of biomedical research. We previously developed a stochastic computer model to examine some of the key pathways involved in the aggregation of amyloid-beta (Aβ) and the micro-tubular binding protein tau. Here we show how we extended this model to include the main processes involved in passive and active immunisation against Aβ and then demonstrate the effects of this intervention on soluble Aβ, plaques, phosphorylated tau and tangles. The model predicts that immunisation leads to clearance of plaques but only results in small reductions in levels of soluble Aβ, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against Aβ. Since, soluble Aβ, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against Aβ may not be effective unless it is performed very early in the disease process or combined with other therapies.
Contributors
Carole Proctor

Metadata information

is
BioModels Database MODEL1212030000
BioModels Database BIOMD0000000488
isDerivedFrom
BioModels Database BIOMD0000000286
BioModels Database BIOMD0000000462
isDescribedBy
PubMed 24098635
hasTaxon
Taxonomy Homo sapiens
hasProperty
Human Disease Ontology Alzheimer's disease
Mathematical Modelling Ontology Ordinary differential equation model
hasPart
Pathway Ontology Alzheimer disease pathway
Curation status
Curated
Original model(s)
Proctor2012_GSK3_p53_AlzheimerDisease_Immunisation_Day4
Name Description Size Actions

Model files

BIOMD0000000488_url.xml SBML L2V4 representation of Proctor2013 - Effect of Aβ immunisation in Alzheimer\s disease (deterministic version) 183.07 KB Preview | Download

Additional files

BIOMD0000000488.vcml Auto-generated VCML file 223.00 KB Preview | Download
BIOMD0000000488.png Auto-generated Reaction graph (PNG) 4.78 MB Preview | Download
BIOMD0000000488.pdf Auto-generated PDF file 745.86 KB Preview | Download
BIOMD0000000488_urn.xml Auto-generated SBML file with URNs 182.58 KB Preview | Download
BIOMD0000000488-biopax3.owl Auto-generated BioPAX (Level 3) 371.42 KB Preview | Download
BIOMD0000000488.sci Auto-generated Scilab file 67.00 bytes Preview | Download
BIOMD0000000488.svg Auto-generated Reaction graph (SVG) 421.90 KB Preview | Download
BIOMD0000000488.xpp Auto-generated XPP file 28.96 KB Preview | Download
BIOMD0000000488-biopax2.owl Auto-generated BioPAX (Level 2) 209.34 KB Preview | Download
BIOMD0000000488.m Auto-generated Octave file 40.00 KB Preview | Download

  • Model originally submitted by : Carole Proctor
  • Submitted: Dec 3, 2012 9:44:56 AM
  • Last Modified: May 8, 2017 6:28:04 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 8, 2017 6:28:04 PM
    • Submitted by: Carole Proctor
    • With comment: Current version of Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (deterministic version)
  • Version: 1 public model Download this version
    • Submitted on: Dec 3, 2012 9:44:56 AM
    • Submitted by: Carole Proctor
    • With comment: Original import of BIOMD0000000488.xml.origin
Curator's comment:
(added: 26 Sep 2013, 18:06:33, updated: 26 Sep 2013, 18:06:33)
Figure 2B (immunisation administered on day 4) of the reference publication has been reproduced here. The model time is in seconds. So, to obtain the result for 12 days, the simulation should be run for 1036800 sec (=12 days). The model was simulated using Copasi v4.10 (Build 55). The plot was generated using Gnuplot.