While scientists are not yet sure how it works, they have linked a new protein to Alzheimer's disease. Called TDP-43, the protein is different from the amyloid and tau that make up the sticky brain plaques and tangles that characterize Alzheimer's. The researchers have not yet ascertained whether TDP-43 causes the disease or develops as a result of it.
For now, "we really need to understand what this protein is doing and its relationship to other proteins," said the study's lead author, Dr. Keith Josephs, a professor of neurology at the Mayo Clinic in Rochester, Minn. He said that everyone has the protein, but the abnormal form is found "in different parts of the cell and in ball-like deposits in certain areas in the brain. It's already been linked to amyotrophic lateral sclerosis, or Lou Gehrig's disease, and frontotemporal dementia."
In the study on aging based at the Mayo Clinic, researchers looked for TDP-43 it in brain samples from 342 people in a study of aging at Mayo. All of them had amyloid plaques in the brain, but many did not have dementia symptoms before they died. Of the total number of participants, 195, or 57 percent, had the abnormal protein. Less than 5 percent of the healthy general population would be expected to have it.
The discovery, which was discussed recently at the Alzheimer's Association International Conference in Copenhagen, could provide a new target for developing drugs and other treatments for Alzheimer's, the most common form of dementia. The study, which also described a new type of brain imaging that can show tau tangles in living people for the first time, could explain why many people have plaques and tangles in their brain yet show no symptoms of the disease. Autopsies on 342 brains revealed that people who had the new protein were 10 times more likely to have been mentally impaired when they died than those without it.
Previously, the only accurate diagnosis of Alzheimer's disease came after death, when brains were examined for amyloid and tau during an autopsy. Now there are methods to use imaging to reveal amyloid on brain scans, and an experimental product from Eli Lilly & Co. can do the same for tau. According to Dr. Clifford Jack, a Mayo Clinic dementia expert, tau correlates better with symptoms than amyloid does. Laurie Ryan of the National Institute on Aging, which funded both studies, agreed that the study was important in that it would help diagnose Alzheimer's and enroll people in studies testing treatments.
The analysis of tau in the brain of people with Alzheimer's was described by researchers from Massachusetts General Hospital. After performing scans on 56 older people believed to be cognitively normal, they found that tau buildup in several brain regions correlated with memory decline. Of those who had the protein, 98 percent had dementia symptoms at the time of their death, versus only 81 percent of those without the protein.
How the new protein might be connected to Alzheimer's is uncertain. According to Josephs, "It's possible that it takes a while to get this protein. Maybe you have to have Alzheimer's developing for 25 years before this protein comes into play," Josephs suggested.
Dr. Anton Porsteinsson, director of the Alzheimer's Disease Care, Research and Education Program at the University of Rochester School of Medicine in Rochester, N.Y., noted that the protein in question has been linked to other brain diseases. "Does this maybe mean that neurodegenerative disorders are part of a broader continuum?" asked Porsteinsson, who reviewed the findings of the new study. He added that the diseases may share a similar cause or similarities in their later stages.
Josephs said he plans on continuing research into the role this protein plays in Alzheimer's.