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The Alzheimer's research field is branching out. After decades focusing on abnormal protein clusters and dying nerve cells in the brain, scientists are now seeking other factors that precede impaired thinking and memory loss. NPR's Jon Hamilton reports from the Alzheimer's Association Conference in San Diego.
JON HAMILTON, BYLINE: Sticky amyloid plaques and tangled fibers called tau are the hallmarks of Alzheimer's. Yet treatments to remove these toxic proteins from the brain have yet to halt the disease. So at the Alzheimer's meeting this week, a team from Seattle is presenting a study designed to identify other targets.
Dr. C. Dirk Keene is a neuropathologist at the University of Washington.
C DIRK KEENE: What we're trying to do with this study is to look at cell vulnerability early on in disease, before they have plaques and tangles, before they have cognitive impairment. That's our ultimate goal.
HAMILTON: The study analyzed more than 1 million cells from 84 brains. Those brains were donated by people in Alzheimer's research projects run by the University of Washington and Kaiser Permanente. Keene says the researchers looked at more than 100 types of cells.
KEENE: We're also looking across many different donors who are at all different stages of disease, even including those who have none, so that we can pinpoint what's happening from the earliest levels all the way through to people with advanced disease.
HAMILTON: The effort is funded by the National Institute on Aging and grew out of the federal BRAIN Initiative launched by President Obama in 2013.
Ed Lein, a senior investigator at the Allen Institute for Brain Science, says the project began with a sobering realization.
ED LEIN: If we want to treat diseases of an extremely complex cellular organ, you need to understand that organ much better than we do.
HAMILTON: So Lein says the team spent years studying cells in healthy brains before looking at brains affected by Alzheimer's.
LEIN: We've defined what normal adult brain looks like, and now we can use that knowledge and look for changes that are happening in specific kinds of cells.
HAMILTON: At the Alzheimer's meeting, the team described what they found in the cortex, an area involved in memory and thinking. Lein says one finding was that neurons were much more likely to die if they made connections within the cortex itself rather than connecting to distant areas of the brain.
LEIN: What we're seeing is a profound effect on cortical circuitry that very plausibly is the reason that we have cognitive decline as this circuitry is affected.
HAMILTON: If so, a treatment designed to protect those vulnerable neurons might prevent cognitive decline. The team also found changes linked to inflammation. Lein says Alzheimer's was associated with a proliferation of certain immune cells and a type of cell that responds to injury.
LEIN: So while the neurons are lost, the nonneuronal cells are actually increasing in their proportions and changing very much in their states.
HAMILTON: The finding supports the idea that inflammation plays an important role in Alzheimer's and that anti-inflammatory drugs might help protect the brain. Lein says the Seattle team hopes other scientists will use its detailed information about brain cells to come up with new treatments for Alzheimer's.
LEIN: We've created a public resource now, an open access resource, where the whole community can come. And they can look at this data. They can mine it to speed up progress in the field as a whole.
HAMILTON: Speeding up progress is one reason Kyle Travaglini of the Allen Institute jumped at the chance to work on the Alzheimer's project.
KYLE TRAVAGLINI: My grandmother started developing Alzheimer's disease when I was just going off to college.
HAMILTON: Travaglini says the Seattle effort is unusual because it isn't based on an existing idea about what causes Alzheimer's.
TRAVAGLINI: It's, like, looking at the same disease that everyone has been looking at but an entirely different way.
HAMILTON: And he says that's what the field needs right now.
TRAVAGLINI: Everything we discover could help a lot of people and maybe not even that far off in the future.
HAMILTON: The Alzheimer's meeting runs through Thursday.
Jon Hamilton, NPR News, San Diego.
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