Cerebrospinal fluid’s immune system is ‘drastically altered’ in people with cognitive impairment such as Alzheimer’s disease, a new study suggests. Photo by Gerd Altmann/Pixabay
Dec. 13 (UPI) — The fluid barrier between the brain and skull provides immune protection, as well as cushioning and nutrients — and this fluid’s immune system is “drastically altered” in people with cognitive impairment such as Alzheimer’s disease, a new study suggests.
The researchers said their discovery about cerebrospinal fluid — and how immune cells in it become dysregulated and ‘a little angry’ as people age — provides a new clue to the process of neurodegeneration.
And it may help treat inflammation of the brain — or diagnose the level of such inflammation in people who have dementia.
Findings from the study, led by researchers at Northwestern University Feinberg School of Medicine, were published Tuesday in the journal Cell.
Researchers also are sharing their data publicly online.
“We now have a glimpse into the brain’s immune system with healthy aging and neurodegeneration,” David Gate, the study’s lead author and assistant professor of neurology at Northwestern University Feinberg School of Medicine, said in a news release.
According to the researchers, little is known about how cerebrospinal fluid immunity is altered with aging or from neurodegenerative disease.
So, they used a technique called “single-cell RNA sequencing” to examine cerebrospinal fluid taken from the spines of 45 cognitively normal subjects who ranged from 54 to 82 years old, isolating their immune cells.
Next, the scientists compared this group to 14 people who were cognitively impaired, as was determined by their poor scores on memory tests.
The research team, including scientists from Stanford University, saw genetic changes in the cerebrospinal immune cells in older healthy individuals that made the cells appear more activated and inflamed with advanced age, the release said.
“The immune cells appear to be a little angry in older individuals,” Gate said in the release. “We think this anger might make these cells less functional, resulting in dysregulation of the brain’s immune system.”
As for the group of people who were cognitively impaired, the researchers found that inflamed T-cells cloned themselves and flowed into the cerebrospinal fluid and brain as though they were following a radio signal.
These cells had too much of a cell receptor, called CXCR6, that acts as an antenna, the release said. This receptor receives a signal, CXCL16, from the degenerating brain’s microglia cells to enter the brain.
“It could be the degenerating brain activates these cells and causes them to clone themselves and flow to the brain,” Gate said. “They do not belong there, and we are trying to understand whether they contribute to damage in the brain.”
The next step is to try to block that radio signal, or stop the antenna from receiving that signal from the brain.
“We want to know what happens when these immune cells are blocked from entering brains with neurodegeneration,” Gate said.
Gate’s laboratory will continue to explore the role of cerebrospinal fluid’s immune cells in brain diseases such as Alzheimer’s, and also will expand to include diseases such as amyotrophic lateral sclerosis, or ALS, the release said.
