Mayo links abnormal protein in brain to Alzheimer's, opening door to new research

A major discovery by a group of Mayo Clinic researchers may bring scientists closer to predicting and treating Alzheimer's disease, a debilitating illness that affects millions of people and their families.

The Mayo team, which presented its findings at an international conference on Wednesday, has uncovered a new link between a protein and Alzheimer's that could push research in new directions.

"Alzheimer's disease symptoms have been typically thought to be produced by plaques and tangles," said Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer's disease Research Center. "Now these folks have documented that there's a third element that contributes to Alzheimer's symptoms."

The protein, known as TDP-43, is normally found in the brain. But what Mayo researchers found is that when it becomes abnormal — chemically different and bunched up — a patient is more likely to show symptoms of Alzheimer's, explained Dr. Keith Josephs, who headed the research team's four-year study.

The next step is for researchers to come up with a test to identify the abnormal protein in a living patient and then develop drugs that can target it, Josephs said. It likely will be "another few years" before researchers come up with a test to detect the third protein, he said. As for treating it, "I think we're a ways out."

Alzheimer's is an incurable, progressive, brain-killing disease and the leading cause of dementia. According to the Alzheimer's Association, more than 5 million Americans are living with the disease and about 500,000 people die each year because they have it. It is the sixth-leading cause of death in the United States.

Advances in Alzheimer's research are "a major, major deal," Josephs said. "The population is aging and this is a disease of age. It's extremely rare for folks in their 30s and 40s to get Alzheimer's but it really exponentially increases after you get to the age of 60 to 65," he said.

Josephs said his team looked at brain samples from 342 people who had amyloid and tau proteins in their brain. "Some of those patients exhibited the symptoms of the disease and some did not," he said. Of those patients, 195 of them — 57 percent — had the abnormal third protein, Josephs said.

"Of the patients who had this third protein, their brains had shrunken more, had more memory loss and were 10 times more likely to have exhibited signs of this disease than those who didn't have the protein. That's the most significant find of the study," Josephs said.

"I think the Alzheimer's community was becoming dejected because their efforts at treating the disease have all failed essentially because their efforts focused on one of the two previously known proteins," he said. "I think the link of the TDP-43 protein injects new life into research because now we have another protein to focus on. I don't think focusing just on TDP-43 is going to be the answer. I think it might be a combination of tau and TDP."

Josephs and Petersen agree there's "much more work to be done," following the Mayo team's discovery.

"It looks like it's a cause, but I would be uncomfortable saying that," Josephs said. "We can't say if we give someone this protein that they're going to get the disease. It doesn't work that way with any of these three proteins."

"So it could be that TDP-43 is beginning to do something a decade or decades before but not until a certain threshold does its effect becomes significant. So is it too late by the time patients come in with memory loss? How far back do we need to go?"

Josephs said the abnormal protein has previously been linked to amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease, and researchers likely already are working on how to test for it.

"If Lou Gehrig's folks are closer to finding a way to identify the protein, then hopefully we can use the same technology to identify the protein for Alzheimer's," he said. "But what we don't know is whether it's in the same form and that's what I'm working on right now. We just don't know if it's identical in both diseases."

"I don't want to give people false hope, but if in five years or a decade we have a test for this and a treatment, then you're going to go into your doctor and do this test," he said. "And if you have TDP-43, your doctor will say, 'It seems you're at risk and here's a tablet that you might want to take and you're good to go.' That's the fairy tale that I want. But that's where we have to get to."

The Mayo researchers presented their discovery at the Alzheimer's Association International Conference in Copenhagen. Also at the conference, a new type of brain imaging that can show tau tangles in living people for the first time was described by other researchers.

"It gives us a new target and possible additional treatment," he said, noting that Alzheimer's symptoms are complex and caused by multiple factors. "It may take a cocktail of treatments to ultimately treat Alzheimer's symptoms and an important third element."

The Associated Press contributed to this report.