Researchers identify new 'immune culprit' in Alzheimer's disease

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
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.

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Researchers also are sharing their data publicly online.

"We still do not fully understand neurodegenerative diseases like Alzheimer's disease. Recently, we have learned that the immune system might be involved," David Gate, the study's lead author and assistant professor of neurology at Northwestern University Feinberg School of Medicine, told UPI via email.


According to Gate, the study offers new information on the role of the immune system in patients living with cognitive impairment, which is a symptom of Alzheimer's disease.

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"We have also learned from this study that the immune system of the brain changes as we age. There is potential to target this immune system to promote healthy brain aging," he said.

The researchers 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.

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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, a news release said.

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.


"We uncovered a signaling mechanism that allows certain immune cells to traffic to the brain. We believe this signaling can be disrupted to alter these cells' ability to home to the brain," Gates said.

And these results suggest that targeting the immune system could be beneficial for diseases like Alzheimer's, he said.

But potential therapies are not close at hand.

"As with any therapeutic development, it will take considerable time to design molecules that target this signaling pathway and to test therapeutics before they go into patients," Gate said. "Yet, identifying the target, as we've done here, is the first step in that process."

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.

Gate told UPI that the researchers have been focused on this area of biology for the past five years, and some of their findings have been unanticipated.

"We are continually surprised by our ability to identify distinct immune system changes in patients. Perhaps most surprising is that some of these patients have very early-stage cognitive impairment, and we can detect their immune changes using our sensitive methods," Gate said.


He added: "This suggests to us that these immune system changes are some of the first to occur in patients and give promise to the idea that we may be able to use immune system measurements to detect diseases in patients before they progress to aggressive dementia."

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