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Rusty Gage and Carol Marchetto
Rusty Gage and Carol Marchetto study brain cells at the Salk Institute. Gage will lead one of three teams taking part in a $43 million research initiative created by the American Heart Institute and the Allen Institute’s Paul G. Allen Frontiers Group. (Salk Institute Photo)

Medical researchers know all about the blood-brain barrier, but Seattle’s Allen Institute and the American Heart Association have selected three teams to participate in a $43 million initiative to study the blood-brain connection.

The American Heart Association-Allen Initiative in Brain Health and Cognitive Impairment initiative, launched in May, is aimed at merging research focusing on the brain and on the blood circulation system to develop a new understanding of age-related brain disorders such as Alzheimer’s disease — and find new ways to counter such disorders.

Today the heart association and the Paul G. Allen Frontiers Group, a division of the Allen Institute, announced which researchers will take part in the effort. The three teams are headquartered at the Salk Institute for Biological Studies and the Stanford University School of Medicine in California; and at University Hospitals Cleveland Medical Center in Ohio.

“To make a difference in Alzheimer’s disease and other cognitive disorders, we have to go beyond incremental research steps to innovative ideas and partnerships that will upend how we approach brain health and decline,” Kathryn Richmond, director of the Allen Frontiers Group, said today in a news release. “We feel the neuroscientists and cardiologists leading these teams have exciting approaches and the expertise needed to have a significant and near-term impact on these devastating diseases.”

Ivor Benjamin, president of the American Heart Association and director of the Cardiovascular Center at the Medical College of Wisconsin, said the blood-brain initiative will represent “an exciting next step in our ongoing commitment to bridging the science of vascular and brain health through revolutionary, out-of-the-box thinking.”

Alzheimer’s disease and other age-related types of dementia will be the initiative’s prime targets. The number of people affected by such maladies is projected to rise to more than 75 million people worldwide by 2030, in part because medical progress is addressing other causes of mortality. In contrast, most types of dementia can’t currently be cured, although some therapies have been developed to slow the progress of symptoms.

The three research teams will investigate potential avenues to better treatments that involve the blood system.

“The questions we are asking in this project are on a frontier that’s really unknown,” said the Salk Institute’s president, Rusty Gage, a neuroscientist who’s leading one of the teams. “How do we age, and why do some people age differently? I’m hopeful that we will reach a coherent answer to that question. We’re all going to age, and through our work we want to provide a map for healthy aging.”

Here’s a quick look at the three potential paths on the blood-brain frontier:

  • Salk’s research team will study aging and diseased neurons using lab-grown human brain tissue, or organoids, as well as marmosets as a primate model for cognitive aging. The eight-year, $19.2 million project will focus on the hypothesis that age-related brain disorders are triggered not by a single event, but by a failure of complex interwoven biological systems that start to break down with age. Understanding how those systems interact could highlight pathways for better treatments.
  • Stanford’s team, led by neurologist Tony Wyss-Coray, has found that blood or plasma from young animals or humans can counter brain aging in old mice, and may reverse the symptoms of mild Alzheimer’s disease. The four-year follow-up project will take a close look at proteins and other molecules that accumulate in blood due to aging, obesity and vascular disease, and look for ways to neutralize disease-causing factors using treatments that mimic the beneficial effects of young blood.
  • The Ohio team is led by Mukesh Jain, a cardiologist at University Hospitals Cleveland Medical Center and Case Western Reserve University. The four-year project will explore how red blood cells and the inner linings of small blood vessels work together to drive brain health as well as age-related cognitive disease.  Researchers will test whether new types of therapies can restore the proper function of blood-brain connections affected by disease. The team includes researchers from University Hospitals Cleveland Medical Center as well as Cleveland Clinic, Johns Hopkins University and the University of Pennsylvania.

The $43 million for the initiative will come from the Allen Frontiers Group and the heart association, plus other contributors including the Oskar Fischer Project and the Henrietta B. and Frederick H. Bugher Foundation.

Allan Jones, president and CEO of the Allen Institute, said the initiative serves as a “clear testament” to the scientific legacy of billionaire Paul Allen, who founded the institute 15 years ago and passed away last month.

Allen, who also was a co-founder of Microsoft, contributed $500 million to establish and sustain the institute that bears his family’s name, in part because his own mother suffered from Alzheimer’s disease.

“Paul inspired all of us every day to tackle hard problems that require systematic, comprehensive approaches to solve,” Jones said, “and these new research teams are a perfect example of that way of thinking about mysteries in science and human health.”

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