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Connecting the dots of Alzheimer’s disease

Stanford engineer Ellen Kuhl is using computer modeling to provide insight into the progress of neurodegenerative diseases like Alzheimer's.

Some people may follow a football team, others may follow their favorite television streaming series. For Ellen Kuhl, PhD, a professor of mechanical engineering at Stanford, her passion lies in following proteins.

In a recent Stanford news article, Kuhl explains how her team developed a computer simulation to track the spread of defective proteins in the brain. These proteins contribute to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's and Lou Gehrig's disease.

As stated in the article:

The group knew that each of the three diseases they were studying produced hallmark clumps of defective, misfolded proteins that build up in the brain. To see how those toxic clumps spread over time, Kuhl and her colleagues looked at brain slices taken from people who died after developing one of the three diseases. Prior researchers had stained those brain slices to reveal the presence of the various proteins of interest.

When Kuhl’s team put the resulting data into a computer, they also did the mathematical modeling to simulate how the pattern of defective proteins spreads from the relatively sparse clumps in people who were early in the disease to much more widespread clumping in people with advanced disease – a process that can take up to 30 years.

Their findings are captured in the video below. (It goes fast — to get the most out of the video, read the description below first).

Kuhl describes this spreading of defective proteins like a domino effect — once one protein has misfolded, it's only a matter of time until its neighbors do as well. But how these proteins misfold in the first place and then spread that mutation is still a mystery.

"The real challenge is that cell death from toxic proteins occurs, years, if not decades, before the first symptoms begin to show," Kuhl says.

To share her data with other labs, Kuhl plans on making a modeling software called the Living Brain Project that will be available to scientists all over the world. That way, neuroscientists can learn more about how these diseases progress and, eventually, catch the misfolded proteins before they wreak too much havoc.

Unfortunately, Alzheimer's and other neurodegenerative diseases are not going away any time soon. Kuhl describes the impact this work will have on the future of medicine:

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.

Photo by sbtlneet

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