Team Simulates how Alzheimer’s disease spreads through the brain

For the first time, scientists have built up a computer simulation of how clusters of defective proteins in neurodegenerative illnesses like Alzheimer’s spread through the brain, a great part of the time in stealth mode, over as long as 30 years.

A Stanford-led team has created a new computer model that shows how amyloid beta proteins spread though the brain in dementia cases. Credit: Courtesy Living Matter Lab, Stanford University

For the first time, scientists have built up a computer simulation of how clusters of defective proteins in neurodegenerative illnesses like Alzheimer’s spread through the brain, a great part of the time in stealth mode, over as long as 30 years.
The simulations focus on Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), but the scientists believe their technique is general enough to work for other brain disorders that involve misshapen proteins, including chronic traumatic encephalopathy.

“We hope the ability to model neurodegenerative disorders will inspire better diagnostic tests and, ultimately, treatments to slow down their effects," said Stanford mechanical engineer Ellen Kuhl said.

Scientists knew that each of the three diseases they were studying produced hallmark clusters of defective, misfolded proteins that build up in the brain. To know how those toxic clumps spread over the long run, scientists took a gander at brain slices taken from individual who died aafter developing one of the three diseases. Earlier researchers had recolored those brain slices to uncover the presence of the different proteins of interest.
Computer simulation shows how two forms of Alzheimer’s disease spread through the brain over a 30-year period. The orange shading shows how clumps of defective amyloid-beta proteins form memory-destroying plaques. The blue shading shows how defects involving the tau protein follow a different progression. The final sequences show how each of these contagions come to engulf the brain. Credit: Stanford University
At the point when scientists put the subsequent information into a computer, they additionally did the scientific demonstrating to mimic how the pattern of damaged proteins spreads from the generally inadequate clumps in individuals who were in the malady to substantially more across the board clumping in individuals with advanced illness – a procedure that can take up to 30 years.
Kuhl said, “Imagine a domino effect. What our model does is connect the dots between the static data points, mathematically, to show disease progression in unprecedented detail.”
In the case of Alzheimer’s disease, the scientists modeled the progression of two misfolding proteins – known as tau and amyloid beta – both of which change shape and form toxic clumps in the brains of people with the disease. Prior researchers had stained brain slices for both proteins and, with the new model, Kuhl’s team was able to create two simulations showing the different way that each of these variants of that disease spread.
Neuroscientists do not know precisely how one clump of defective proteins affects its neighbors to spread the misfolding, although Kuhl said there are three prevailing theories. The virtue of the model, she said, is that it predicts the path of the disease regardless of which theory is correct.
Kuhl now plans to work with neuroscientists to better understand the mechanisms of how the proteins misfold. These insights would improve their model and perhaps lead to better ways of diagnosing the disease while it is still in stealth mode.
Kuhl said, “The real challenge is that cell death from toxic proteins occurs years, if not decades, before the first symptoms begin to show. Given the aging of the population, by mid-century 135 million people worldwide will have some form of dementia. We have to find new ways to spur research toward diagnostics and interventions, and computer modeling can play a key role in identifying new therapeutic targets.”
The study is published in the journal Physical Review Letters.

Provided By: Stanford University

Reference: Tech Explorist

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Scien-Tech News: Team Simulates how Alzheimer’s disease spreads through the brain
Team Simulates how Alzheimer’s disease spreads through the brain
For the first time, scientists have built up a computer simulation of how clusters of defective proteins in neurodegenerative illnesses like Alzheimer’s spread through the brain, a great part of the time in stealth mode, over as long as 30 years.
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