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12:01 AM EDT/Friday, April 17, 2009
Contact: Donna Krupa
Newsroom: (504) 670-4525 or 4526
Office: (301) 634-7209
Cell: (703) 967-2751
dkrupa@the-aps.org
A
Computational Model Examines the Pathways of Alzheimer’s That
Strikes at the Young
NEW ORLEANS—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.
Conclusion
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.
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Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease. The American Physiological Society (APS;
www.The-APS.org/press) has been an integral part of this discovery
process since it was established in 1887.
NOTE TO EDITORS: The APS annual meeting is part
of the Experimental Biology 2009 (EB ’09) gathering and will be held April
18-22, 2009 at the New Orleans Convention Center. To schedule an interview
with Ms. Glaw, please contact Donna Krupa at 301.634.7209 (office),
703.967.2751 (cell) or
DKrupa@the-APS.org.
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