Computational model examines the pathways of Alzheimer's that strikes at the young
Alzheimer's disease (AD) is a tragic disease that robs an individual of their memory and mental capacity. One in eight people over the age of 65 now suffer from the disease and one in two people over 85 are diagnosed with the disease. Contrary to popular belief, Alzheimer's does not only affect the elderly. Familial Alzheimer's disease (FAD), an offshoot of the disease, affects those as young as 30. The Study
Alzheimer's is a complex disease, and so too are the attempts to explain it. One way to understand how the brain works to cause the disorder is by using computational modeling, (a series of equations) to characterize an individual aspect that is important to the disease. Biomedical engineers Lydia S. Glaw and Thomas C. Skalak, Ph.D., of the Department of Biomedical Engineering, University of Virginia, Charlottesville, have created a model to examine the role of certain proteins in the development of the disease. Their findings are contained in the study entitled A Computational Model of the Role of Presenilin-1 and Glycogen Synthase Kinase-3 in Familial Alzheimer's Disease. They will present their findings at the 122nd Annual Meeting of the American Physiological Society (APS; www.the-aps.org/press), which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.
The researchers constructed a simple computational model to measure plaques and tangles and their influence in causing FAD. The model tested the hypothesis that certain variables—genetic mutations in proteins and "tau" tangles—might be predicative of the development of the disease. The main hypothesis that the model tested was the idea that GSK3 is a link between amyloid beta buildup and tau tangle development.
Brain Plaque: A Major Instigator?
The proteins presenilin-1 (PS1) (a mutated gene found in familial AD) and glycogen synthase kinase (GSK-3) (a protein) and amyloid beta (Aβ) plaque (amino acids that are found in large quantity in AD) were studied to quantitatively examine their roles in the development of Alzheimer's pathology. The elements (in the form of existing research data) 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 model is a first-of-its-kind approach to modeling, understanding and predicting Alzheimer's pathways.
Results: No Link Between A Protein and Plaques, Tangles
GSK3 had a large effect on tangle formation, but very little on the plaques. 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 may be able to cause those changes. Nor was there any link found between amyloid beta plaque and tau tangles. The main conclusion of the model so far is that no single change to the system can cause Alzheimer's disease. Multiple changes, such as a PS1 mutation combined with GSK3 over-activation can, however. A multi-pronged approach to treating the disease may be best.
Glaw's model can be used for additional pathway analysis. She views modeling as a useful way for better understanding this complex, multi-layered disease.
Source: American Physiological Society
- Mouse gene suppresses Alzheimer's plaques and tanglesWed, 11 Nov 2009, 15:13:10 EST
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- Study shows antibody therapy clears Alzheimer's plaques in miceWed, 5 Dec 2012, 13:07:02 EST
- Alzheimer's Disease: New Small Molecule Approach To Treatmentfrom Science DailyFri, 17 Apr 2009, 21:35:40 EDT
- Computational Model Examines The Pathways Of Alzheimer's That Strikes At The Youngfrom Science DailyFri, 17 Apr 2009, 10:21:36 EDT
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