Evidence map›Paper›PMID 24098635›Full record

ArticlePloS one2013

Investigating interventions in Alzheimer's disease with computer simulation models.

Carole J Proctor, Delphine Boche, Douglas A Gray, James A R Nicoll

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. When Does Alzheimer's Disease Really Start? The Role of Biomarkers.International journal of molecular sciences · 2019
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. BioModels: Content, Features, Functionality, and Use.CPT: pharmacometrics & systems pharmacology · 2015
    Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Carole J ProctorInstitute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Delphine Boche
Douglas A Gray
James A R Nicoll

Funding

Biotechnology and Biological Sciences Research CouncilCIHRMedical Research Council G0501033
6 · The paper itself

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.

Indexed as

Models, BiologicalAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, MonoclonalComputer SimulationDrug Evaluation, PreclinicalHumansImmunizationImmunotherapySystems Biologytau ProteinsAmyloid beta-PeptidesAntibodies, Monoclonaltau Proteins

Identifiers

PMID24098635
PMCPMC3782376

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.