%0 Journal Article
%T Aggregation, impaired degradation and immunization targeting of amyloid-beta dimers in Alzheimer¡¯s disease: a stochastic modelling approach
%A Carole J Proctor
%A Ilse Sanet Pienaar
%A Joanna Elson
%A Thomas BL Kirkwood
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-32
%X Our model demonstrates for the first time that even a slight decrease in the clearance rate of A£¿42 monomers is sufficient to increase the chance of dimers forming, which could act as instigators of protofibril and fibril formation, resulting in increased plaque levels. As the process is slow and levels of A¦Â are normally low, stochastic effects are important. Our model predicts that reducing the rate of dimerisation leads to a significant reduction in plaque levels and delays onset of plaque formation. The model was used to test the effect of an antibody mediated immunological response. Our results showed that plaque levels were reduced compared to conditions where antibodies are not present.Our model supports the current thinking that levels of dimers are important in initiating the aggregation process. Although substantial knowledge exists regarding the process, no therapeutic intervention is on offer that reliably decreases disease burden in AD patients. Computer modelling could serve as one of a number of tools to examine both the validity of reliable biomarkers and aid the discovery of successful intervention strategies.
%K Alzheimer¡¯s disease
%K Amyloid-beta
%K Dimers
%K Down¡¯s syndrome
%K Intervention
%K Immunotherapy
%K Mathematical model
%K Protein aggregation
%K Stochastic simulation
%U http://www.molecularneurodegeneration.com/content/7/1/32/abstract