Alzheimer's disease is one of the most dreaded and debilitating illnesses one can develop. Currently, the disease afflicts 6.5 million Americans and the Alzheimer's Association projects it to increase to between 11 and 16 million, or 1 in 85 people, by 2050.
Cell death in the brain causes one to grow forgetful, confused and, eventually, catatonic. Recently approved drugs provide mild relief for symptoms but there is no consensus on the underlying mechanism of the disease.
"We don't know what the problem is in terms of toxicity," said Joan-Emma Shea, professor of chemistry and biochemistry at the University of California, Santa Barbara (UCSB). "This makes the disease difficult to cure."
Accumulations of amyloid plaques have long been associated with the disease and were presumed to be its cause. These long knotty fibrils, formed from misfolded protein fragments, are almost always found in the brains of diseased patients. Because of their ubiquity, amyloid fibrils were considered a potential source of the toxicity that causes cell death in the brain. However, the quantity of fibrils does not correspond with the degree of dementia and other symptoms.
New findings support a hypothesis that fibrils are a by-product of the disease rather than the toxic agent itself. This paradigm shift changes the focus of inquiry to smaller, intermediate molecules that form and dissipate quickly. These molecules are difficult to perceive in brain tissue.
Shea's group uses computer simulations to understand the formation of toxic entities in the brain. Since 2007, Shea has run thousands of simulations of amyloid peptides using the Ranger supercomputer at the Texas Advanced Computing Center (TACC) to better understand the structure, formation and behavior of amyloid accumulations.
"We can identify the important structures or conformations that are adopted by these peptides at a resolution that exceeds what can be done experimen
|Contact: Faith Singer-Villalobos|
University of Texas at Austin, Texas Advanced Computing Center