The adult brain weighs between 1.3 and 1.4 kilos, but it seems lighter because it is surrounded by cerebrospinal fluid (CSF) and floats on this substance, which also provides nutrients to the brain and forms a barrier between this organ and the skull, protecting it against possible head trauma, but also against infections and pathogens such as bacteria, viruses, fungi and parasites, thanks to the immune cells it contains.
This immune function of the CSF is very important, but less well understood, although now a new study from Northwestern Medicine has found that cerebrospinal fluid plays a key role in cognitive decline and the development of Alzheimer’s disease. The finding provides a new clue about the neurodegenerative process that leads to the onset of these disorders, said David Gate, an assistant professor of neurology at Northwestern University Feinberg School of Medicine and lead author of the paper.
The results of the study have been published in Cell and show that our immune system dysregulates as we age and that in people with cognitive impairment, such as Alzheimer’s patients, the CSF immune system is significantly different than of healthy individuals.
“Immune cells seem to be a bit angry in older people, which can make these cells less functional”
“Now we can glimpse the brain’s immune system with healthy aging and neurodegeneration,” Gate said. “This immune reservoir could potentially be used to treat inflammation of the brain, or used diagnostically to determine the level of brain inflammation in people with dementia.” “We offer a comprehensive analysis of this important immune reservoir of the healthy and diseased brain,” Gate added, as her team is sharing the data publicly and is searchable online.
Inflamed T cells disrupting the brain’s immune system
Using a sophisticated technique called single-cell RNA sequencing to analyze CSF, the researchers profiled 59 CSF immune systems across an age spectrum by taking CSF from the participants’ spinal cord and isolating their immune cells. In a first phase, they analyzed the CSF in 45 healthy people between the ages of 54 and 83, and during the second part of the study they compared the findings in the healthy group with the CSF in 14 adults with cognitive impairment, who had been diagnosed for obtaining low scores in memory tests.
Gate’s observed genetic changes in CSF immune cells in healthy seniors, which made the cells appear more activated and inflamed with advancing age. “Immune cells seem to be a bit angry in older people,” Gate said. “We think this anger could make these cells less functional, resulting in dysregulation of the brain’s immune system.”
In the cognitively impaired individuals, the inflamed T cells were cloned and flowed into the cerebrospinal fluid and brain as if following a radio signal, Gate said. The researchers found that the cells had an excess of a cellular receptor, CXCR6, which acts like an antenna, receiving a signal, CXCL16, from degenerating brain microglia cells to enter the brain.
“It could be that the degenerating brain activates these cells and causes them to clone and flow into the brain,” Gate explained. “They don’t belong there and we are trying to understand if they contribute to damage in the brain.” The scientist affirms that his “future objective is to block that radio signal, or prevent the antenna from receiving that signal from the brain. We want to know what happens when these immune cells can’t get into the brain with neurodegeneration.” Gate’s lab will continue to explore the role of these immune cells in brain diseases such as Alzheimer’s, and they intend to study other diseases as well, such as amyotrophic lateral sclerosis (ALS).
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