Browse by author
Lookup NU author(s): Dr Carole Proctor, Professor Doug Gray
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 (A beta) 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 A beta and then demonstrate the effects of this intervention on soluble A beta, 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 A beta, phosphorylated tau and tangles. The behaviour of this model is supported by neuropathological observations in Alzheimer patients immunised against A beta. Since, soluble A beta, phosphorylated tau and tangles more closely correlate with cognitive decline than plaques, our model suggests that immunotherapy against A beta may not be effective unless it is performed very early in the disease process or combined with other therapies.
Author(s): Proctor CJ, Boche D, Gray DA, Nicoll JAR
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2013
Volume: 8
Issue: 9
Online publication date: 16/09/2013
Acceptance date: 25/07/2013
Date deposited: 20/11/2014
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: http://dx.doi.org/10.1371/journal.pone.0073631
DOI: 10.1371/journal.pone.0073631
Altmetrics provided by Altmetric
