Your three-pound brain doesn't feel heavy because it floats in a reservoir of cerebrospinal fluid (CSF), which flows around your brain and spinal cord. This fluid barrier between the brain and the skull protects the brain from head impact and provides nutrients to the brain. But, if less well known, the CSF also has another key function: it also provides immune protection to the brain. However, this function has not been fully studied.
In a new study, researchers from Northwestern University's Feenberg School of Medicine in the US found the role of cerebrospinal fluid in cognitive impairment (such as Alzheimer's disease). This finding provides new clues to the neurodegeneration process. The results were published online in the Cell journal on December 13,2022, with the title "Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment". The corresponding author of the paper is Dr. David Gate, Assistant Professor of Neurology at Feenberg School of Medicine, Northwestern University.
This study found that the CSF immune system becomes dysregulated with increasing age. The study also found that the CSF immune system was very different from that of healthy people in people with cognitive impairment (such as Alzheimer's disease).
Gate says, " We can now understand how this brain immune system relates to healthy aging and neurodegeneration. This immune bank (i. e., the cerebrospinal fluid bank) may be used to treat inflammation in the brain, or it may be used as a diagnosis to determine the level of brain inflammation in patients with dementia. We performed a comprehensive analysis of this important immune repertoire of healthy and diseased brains."His team is publicly sharing their data, and the results can be searched online.
To analyze the CSF, the Gate team used a sophisticated technique called single-cell RNA sequencing. They analyzed the CSF immune system of 59 participants from a range of ages by extracting CSF from their spines and separating their immune cells (such as T cells).
The first part of this study explored the CSF of 45 healthy people aged 54 to 83 years. The second part of the study compares the results of these healthy people to the CSF of 14 adults with cognitive impairment (as determined by their poor scores on a memory test).
The Gate team has observed genetic changes in the cerebrospinal fluid immune cells in older, healthy people, which allow these cells to become more active and inflamed with age. Gate says, " The immune cells in the cerebrospinal fluid of older people seem to be a little inflammatory. We suggest that this inflammation may attenuate these cells and cause dysregulation of the brain immune system.”
In cognitively impaired adults, inflamed T cells self-clone and flow into the cerebrospinal fluid and brain as if they follow radio signals, Gate says. The Gate's team found that these cells have a large amount of a cellular receptor, beta-beta-CXCR 6, which acts as an antenna. This receptor receives signals from degenerated brain microglia – CXCL16 for T cells to enter the brain.
Gate says, " It's possible that the degenerated brain activates these immune cells, allowing them to self-clone and flow to the brain. They aren't there, and we're trying to see if they cause brain damage.”
Gate said that his " goal of the future is to block the radio signal, or to inhibit the antennas from receiving signals from the brain. We wondered what happens when these immune cells are blocked into the neurodegenerative brain.”
The Gate lab will continue to explore the role of these immune cells in brain diseases such as Alzheimer's disease. They also plan to expand to other diseases, such as amyotrophic lateral sclerosis (ALS).
