Scientists have developed a computational model to examine the role of certain proteins in the development of Familial Alzheimer's disease (FAD), which affects people as young as 30.
Biomedical engineers Lydia S. Glaw and Thomas C. Skalak, Ph.D., of the Department of Biomedical Engineering, University of Virginia, Charlottesville, constructed the model to measure plaques and tangles and their influence in causing FAD.
AdvertisementThe model tested the hypothesis that certain variables-genetic mutations in proteins and "tau" tangles-might be predicative of the development of the disease.
The model is a first-of-its-kind approach to modeling, understanding and predicting Alzheimer's pathways.
One of the biggest hypotheses tested by the model was the idea that GSK3 is a link between amyloid beta buildup and tau tangle development.
The researchers studied the proteins presenilin-1 (PS1) (a mutated gene found in familial AD) and glycogen synthase kinase (GSK-3) and amyloid beta (A) plaque, to quantitatively examine their roles in the development of Alzheimer's pathology.
The elements were applied to the model, which was constructed of kinetic equations developed from literature searches, and analyzed the interactions of the proteins and complexes under various scenarios.
The researchers found that GSK3 had a large effect on tangle formation, but very little on the plaques.
Also, activating GSK3 was not found to be sufficient to cause changes in the brain to the extent seen in Alzheimer's patients.
However, overproduction of GSK3 as opposed to activation could lead to those changes.
Besides there was no link found between amyloid beta plaque and tau tangles.
They concluded that no single change to the system could cause Alzheimer's disease; instead it was caused by multiple changes, such as a PS1 mutation combined with GSK3 over-activation.
They suggested that a multi-pronged approach to treating the disease may be best.
The findings will be presented at the 122nd Annual Meeting of the American Physiological Society.
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