This isn’t the first study to suggest this therapeutic pathway, but it is the first in-depth analysis of the brain’s immune system. Within this system, the researchers recall the role of the cerebrospinal fluid (CSF) reservoir, which circulates in and around the brain and spinal cord. This liquid barrier between the brain and the skull plays a role of physical protection – once morest shocks-, but performs another critical function, less known: a role of immune protection, which remains poorly understood.
Better understand the role of CSF in Alzheimer’s
The study deciphers this role of CSF in cognitive disorders, including Alzheimer’s disease. Work that offers a new clue to the process of neurodegeneration: the team uses single-cell RNA sequencing to model 59 CSF-associated immune systems from 45 healthy participants; then the researchers compare these results with those of the CSF of 14 adults diagnosed with cognitive disorders. This review finally reveals:
- genetic changes in CSF immune cells in healthy older people, with the cells becoming more active and inflamed with advancing age.
- “Immune cells seem to be a bit angry in older people”, comment the researchers. An activation that might make these cells less functional, leading to dysregulation of the brain’s immune system;
- In the group of participants with cognitive impairment, inflamed T cells are cloned and flood into CSF and brain “as if they were obeying a radio signal”;
- these T cells have an overabundance of a cell receptor – CXCR6 – which acts as an antenna. This receptor receives a signal – CXCL16 – from degenerating brain microglial cells prompting them to enter the brain;
- “It might be that the degenerating brain activates these cells and causes them to clone themselves and flow to the brain. We are working to understand how they contribute to brain damage.”
Scientists thus propose a decryption of the immune system of the brain in healthy aging and in neurodegeneration. With clinical implications: “This immune reservoir might be used to treat brain inflammation or as a diagnostic marker of the level of brain inflammation in patients with dementia.”
“Blocking this radio signal of degeneration or preventing the antenna from receiving this signal might prevent immune cells from entering the brain.”
The team continues to explore the role of these immune cells in brain diseases such as Alzheimer’s disease, but also in other diseases, such as amyotrophic lateral sclerosis (ALS).
