More than a hundred years later, researchers at the University of Wisconsin School of Medicine and Public Health now believe Alzheimer’s may develop in its early stages in the brain’s “white matter,” which coordinates various functions in the central nervous system.
Their study published in PLoS One, the peer-reviewed, open-access journal, involved 43 healthy middle-aged participants who had at least one parent with Alzheimer’s disease. Samples of their cerebrospinal fluid, a clear fluid which surrounds the brain, were acquired through lumbar puncture.
The fluid can be tested for presence of proteins related to Alzheimer’s, namely total tau protein, and the 42-residue form of beta-amyloid protein.
According to Dr. Barbara Bendlin, the lead researcher and assistant professor of medicine (geriatrics) at the UW School of Medicine and Public Health, brain scans given to the participants years later showed that proteins measured in cerebrospinal fluid predicted degeneration in the white matter. This was a surprise because the studied proteins are usually related to degeneration in the brain’s gray matter.
“Brain white matter is made up of structures called myelinated axons, and they form connections in the brain-the telephone wires that let different parts of the brain speak to each other,” she said. “This study suggests that at the earliest stages of Alzheimer’s, these connections are breaking down.”
Bendlin said these findings are significant because they could lead to even earlier diagnosis of Alzheimer’s.
“We studied people who are still healthy, but at increased risk for Alzheimer’s because their parents had or have the disease,” she said. “This study underscores the finding that brain changes in Alzheimer’s probably begin decades before diagnosis, and we expect that we can detect the disease earlier and intervene before memory problems occur.”
While the results are promising, Bendlin said more investigation is needed to determine how degeneration of white matter could lead to future Alzheimer’s cases.
“Because of the way we do our statistical analysis, the results don’t show percentages on how many people show ‘bad’ white matter and we also don’t have a cut-off for what would be considered ‘bad’ or unhealthy white matter as indexed by this type of brain imaging,” she said. “This is something we hope to develop by following people over time and learning what measures will predict who will develop Alzheimer’s in the future.”
“All of the subjects in the study are healthy with normal memory,” Bendlin added. “We are following people to see which participants will show memory declines and to determine what will predict that.”
Bendlin’s research group recently received a $1.5 million grant from the National Institutes of Health to conduct a five-year study of white matter in 160 people. Half of them will have at least one parent who has Alzheimer’s and the other half will not have a family history of the disease.
University of Wisconsin School of Medicine and Public Health