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Scientists Push Plan To Change How Researchers Define Alzheimer's

Apr 10, 2018
Originally published on April 13, 2018 9:16 am

An international coalition of brain researchers is suggesting a new way of looking at Alzheimer's.

Instead of defining the disease through symptoms like memory problems or fuzzy thinking, the scientists want to focus on biological changes in the brain associated with Alzheimer's. These include the plaques and tangles that build up in the brains of people with the disease.

But they say the new approach is intended only for research studies and isn't yet ready for use by most doctors who treat Alzheimer's patients.

If the new approach is widely adopted, it would help researchers study patients whose brain function is still normal, but who are likely to develop dementia caused by Alzheimer's.

"There is a stage of the disease where there are no symptoms and we need to have some sort of a marker," says Eliezer Masliah, who directs the Division of Neuroscience at the National Institute on Aging.

The new approach would be a dramatic departure from the traditional way of looking at Alzheimer's, says Clifford Jack, an Alzheimer's researcher at Mayo Clinic Rochester.

In the past, "a person displayed a certain set of signs and symptoms and it was expected that they had Alzheimer's pathology," says Jack, who is the first author of the central paper describing the proposed new "research framework."

But researchers began to see the flaws in that approach when they took a close look at the brains of people receiving experimental drugs for the disease, Jack says. "About 30 percent of people who met all the appropriate clinical criteria did not have Alzheimer's disease."

Their memory or thinking problems were being caused by something else.

So researchers have been looking for more reliable ways of determining whether someone really has Alzheimer's. And they've focused on the two best-known brain changes associated with the disease.

"What we're seeing now is that Alzheimer's disease is defined by the presence of plaques and tangles in your brain," Jack says. And in this way of thinking, he says, "symptoms become the result of the disease, not the definition of the disease."

Once it was virtually impossible to detect plaques and tangles in a living person. But over time, scientists have developed a number of ways to spot the abnormalities using special brain scans or tests of spinal fluid.

These tests for what are known as biomarkers of Alzheimer's are allowing scientists to do experiments that would have been impossible relying on symptoms alone. "One could, let's say, start preventive treatment five years before the onset of the symptoms," Masliah says.

The new approach has detractors, who argue that it's not yet a reliable replacement for clinical symptoms in research. And proponents have responded to these complaints by including symptom measures in their proposal, and acknowledging that biomarkers are still in an early stage of development.

Proponents have also stressed that the biomarker approach is not yet the right tool for most doctors who treat Alzheimer's patients.

"It's a research framework meant to be tested, a tool for researchers, not for the doctor's office," says Maria Carrillo, chief scientific officer of the Alzheimer's Association.

But Carrillo hopes that when drugs to prevent Alzheimer's finally arrive, biomarker tests can show who should get them.

The proposal, and several commentaries supporting it, appears Tuesday in the April 2018 issue of Alzheimer's & Dementia: The journal of the Alzheimer's Association.

Copyright 2018 NPR. To see more, visit http://www.npr.org/.

STEVE INSKEEP, HOST:

A large coalition of brain researchers has unveiled a plan to redefine Alzheimer's disease. The goal here is to study Alzheimer's by focusing on biological changes in the brain rather than symptoms like memory loss. NPR's Jon Hamilton reports.

JON HAMILTON, BYLINE: The plan offers a new and different way of looking at Alzheimer's. Clifford Jack of the Mayo Clinic says the old way worked like this.

CLIFFORD JACK: A person displayed a certain set of signs and symptoms, and it was expected that they had Alzheimer's pathology.

HAMILTON: Jack says researchers began to see the flaws in that approach when they took a close look at the brains of people receiving experimental drugs for the disease.

JACK: About 30 percent of people who met all the appropriate clinical criteria did not have Alzheimer's disease.

HAMILTON: Their memory or thinking problems were being caused by something else. So Jack says researchers began looking for more reliable ways of determining who really has Alzheimer's.

JACK: What we're saying now is that Alzheimer's disease is defined by the presence of plaques and tangles in your brain.

HAMILTON: Sticky plaques and threadlike tangles of proteins that build up over time. Jack says in this new view, researchers treat these abnormal proteins along with evidence of brain damage as hallmarks of Alzheimer's.

JACK: And symptoms become a result of the disease, not the definition of the disease.

HAMILTON: Eliezer Masliah of the National Institute on Aging says defining Alzheimer's by plaques and tangles also solves another big problem for researchers.

ELIEZER MASLIAH: There is a stage of the disease where there are no symptoms, and we need to have some sort of a marker.

HAMILTON: What scientists call a biomarker. And now there are a range of biomarkers for plaques and tangles. They are detected through special brain scans and tests of spinal fluid. Masliah says that means scientists can now do experiments that would have been impossible relying on symptoms alone.

MASLIAH: One could, let's say, start preventive treatment five years before the onset of the symptoms based on the presence of the biomarkers.

HAMILTON: Scientists outlined the new approach in several papers in the journal Alzheimer's And Dementia. But proponents say the new definition is intended for researchers, not doctors and their patients. That's because current biomarker tests are expensive, often difficult to perform. And, even if they find something, there's still no way to stop the underlying disease. Maria Carrillo is the Alzheimer's Association's chief scientific officer.

MARIA CARILLO: It's a research framework meant to be tested, a tool for researchers, not for the doctor's office.

HAMILTON: But she says a few doctors who specialize in Alzheimer's are already beginning to use tests for plaques and tangles.

CARILLO: Some of those physicians actually are able to incorporate some biomarkers to actually make a more precise diagnosis.

HAMILTON: That can help in some special cases. And Carillo hopes that when drugs to prevent Alzheimer's finally arrive, biomarker tests can show who should get them. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.