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

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Short description
Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (stochastic version)
Extension of a previously published stochastic model (designed to examine some of the key pathways involved in the aggregation of amyloid-beta (A β) and the micro-tubular binding protein tau ( BIOMD0000000286, BIOMD0000000462)) to include the main processes involved in passive and active immunisation against A β and then to demonstrate the effects of this intervention on soluble A β. This is the stochastic version of the model, the deterministic version is BIOMD0000000488

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.

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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 MODEL1704060000
BioModels Database BIOMD0000000634
isDerivedFrom
BioModels Database BIOMD0000000286
BioModels Database BIOMD0000000462
isDescribedBy
PubMed 24098635
hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Human Disease Ontology Alzheimer's disease
hasPart
Pathway Ontology Alzheimer disease pathway
Curation status
Curated
Original model(s)
Newcastle upon Tyne
  • Model originally submitted by : Carole Proctor
  • Submitted: 06-Apr-2017 16:49:14
  • Last Modified: 01-Jun-2017 18:52:20
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 01-Jun-2017 18:52:20
    • Submitted by: Carole Proctor
    • With comment: Current version of Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease (stochastic version)
  • Version: 1 public model Download this version
    • Submitted on: 06-Apr-2017 16:49:14
    • Submitted by: Carole Proctor
    • With comment: Original import of Proctor2013 - Effect of Aβ immunisation in Alzheimer's disease
Curator's comment:
(added: 16 May 2017, 15:16:29, updated: 16 May 2017, 15:16:29)
This model is the stochastic implementation of BIOMD0000000488, which is the deterministic version. The model reproduces figure 2B of the reference publication, we have checked the model simulation using a stochastic simulation method in Copasi v4.19 (Build 140), but have not created a curation figure. Refer to BIOMD0000000488 for the deterministic simulation result.