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

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 i...

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Autores principales:	Carole J Proctor, Delphine Boche, Douglas A Gray, James A R Nicoll
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8caadb27d5ab41cb97fdeff47d23c4c2
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spelling	oai:doaj.org-article:8caadb27d5ab41cb97fdeff47d23c4c22021-11-18T08:54:59ZInvestigating interventions in Alzheimer's disease with computer simulation models.1932-620310.1371/journal.pone.0073631https://doaj.org/article/8caadb27d5ab41cb97fdeff47d23c4c22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098635/?tool=EBIhttps://doaj.org/toc/1932-6203Progress 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.Carole J ProctorDelphine BocheDouglas A GrayJames A R NicollPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73631 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carole J Proctor Delphine Boche Douglas A Gray James A R Nicoll Investigating interventions in Alzheimer's disease with computer simulation models.
description	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.
format	article
author	Carole J Proctor Delphine Boche Douglas A Gray James A R Nicoll
author_facet	Carole J Proctor Delphine Boche Douglas A Gray James A R Nicoll
author_sort	Carole J Proctor
title	Investigating interventions in Alzheimer's disease with computer simulation models.
title_short	Investigating interventions in Alzheimer's disease with computer simulation models.
title_full	Investigating interventions in Alzheimer's disease with computer simulation models.
title_fullStr	Investigating interventions in Alzheimer's disease with computer simulation models.
title_full_unstemmed	Investigating interventions in Alzheimer's disease with computer simulation models.
title_sort	investigating interventions in alzheimer's disease with computer simulation models.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8caadb27d5ab41cb97fdeff47d23c4c2
work_keys_str_mv	AT carolejproctor investigatinginterventionsinalzheimersdiseasewithcomputersimulationmodels AT delphineboche investigatinginterventionsinalzheimersdiseasewithcomputersimulationmodels AT douglasagray investigatinginterventionsinalzheimersdiseasewithcomputersimulationmodels AT jamesarnicoll investigatinginterventionsinalzheimersdiseasewithcomputersimulationmodels
_version_	1718421153538637824

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

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