Alzheimer's study in Seattle makes new findings for future therapies
SEATTLE - Alzheimer’s is a devastating disease with no cure, yet it is the leading cause of dementia for people ages 65 and older. The Center for Disease Control and Prevention (CDC) said Washington had the third-highest Alzheimer’s mortality rate in the nation, according to a 2022 report.
Local scientists are studying new ways of how the world understands the disease and possible treatments.
In the heart of Seattle, some of the world’s most brilliant minds study the brain at the Allen Institute. It’s where scientists research the cellular makeup of the human body’s most complex organ.
"For years, the Allen Institute has created maps to define what are the types of cells that exist within the brain. And now we are putting those maps to work to be able to understand disease. What types of cells are dying or being affected? And that, down the road, could lead to therapeutics," said Mariano Gabitto, an assistant investigator at the Allen Institute.
Researchers at the institute study how various diseases affect the brain and cells. Gabitto and scientist Kyle Travaglini are focused on Alzheimer’s, or AD.
"For over 100 years now, we’ve had these protein pathologies, these plaques and tangles that are building up in the brain that have sort of defined Alzheimer’s disease. And they’re still incredibly useful. I think they’re the best markers we have of the disease, and they’re the basis for some of the therapeutics that we have that are starting to show modest benefits. But I think everyone would acknowledge that we need new kinds of targets to really have those blockbuster impacts," said Travaglini.
AD is a disorder among older adults that slowly ruins memory and thinking skills, ultimately destroying the ability to do simple tasks. The Alzheimer’s Association said about one in 10 older adults in the United States have AD.
"I think in the state of Washington, it’s about 127,000 individuals. So, it is something that really impacts a lot of people, unfortunately," said Travaglini.
Gabitto and Travaglini are major contributors to this study that began about five years ago. Their research has discovered new understandings about cells in the brain when Alzheimer’s begins.
According to the Allen Institute, "Using advanced single-cell genomic technologies and novel machine learning models, the scientists mapped out a timeline of the disease’s cellular and molecular changes. In the process, they identified a specific type of inhibitory neuron (the somatostatin-expressing inhibitory neuron) as one of the earliest cell types that is lost in AD — a surprising discovery that could highlight potential targets for future therapies."
"The work that we are doing is very foundational. It’s trying to look at what is happening in donors that are very early on in their course of disease. What are the kinds of cells that are changing inside of their brains, and then why?" said Travaglini.
Now they’re working to determine why those brain cells are changing or dying as the disease progresses. Finding that answer could lead to the development of new treatments to target and possibly prevent Alzheimer’s early.
"All the study that we did was looking at one particular brain region. Now we are going to look at the entire brain and multiple regions and start seeing do we observe the same changes, or the same cellular types affected," said Gabitto. "If you know what are the early changes that are happening, maybe you can create a therapeutic intervention and maybe prevent the course of the disease."
This groundbreaking study includes more than 3.4 million cells from 84 brains donated by Alzheimer’s patients. It’s in partnership with the University of Washington and Kaiser Permanente.
Allen Institute said this discovery is reportedly the first of its kind in the world.
"We are leading the way on this study," said Gabitto.
Travaglini said he got involved three years ago after his early research became personal.
"When I was entering college, my grandmother had started to develop memory issues and eventually progressed to having dementia. So, I’d been in research in science at that point, but then seeing that made me want to have my career built on understanding what happened to her and trying to come up with ways that we can help people like her in the future," said Travaglini.
"To me, it’s important that science gets to make a change and impact people. We are doing foundational research that can be translated into real advances and therapeutic interventions," said Gabitto.
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