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

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:

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

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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and identified by:
BIOMD0000000488.
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