For many years, scientists have searched for the cause (or causes) of Alzheimer's disease. While a lot of research attention has focused on misfolded proteins as the potential culprit, there have been indications that other things were involved in the neurodegenerative disease, such as neuroinflammation. New research has found that immune signatures in the cerebrospinal fluid (CSF) of Alzheimer's patients is dramatically different from those in unaffected individuals. The findings have been reported in Cell.
"We now have a glimpse into the brain's immune system with healthy aging and neurodegeneration. This immune reservoir could potentially be used to treat inflammation of the brain or be used as a diagnostic to determine the level of brain inflammation in individuals with dementia," suggested corresponding study author David Gate, an assistant professor at Northwestern University Feinberg School of Medicine.
Our sensitive central nervous system, the brain and spinal cord, are bathed in cerebrospinal fluid (CSF). This fluid performs several functions, including physically protecting the central nervous system, as well as aiding in immune protection.
In this study, the researchers used single-cell sequencing to assess the immune cells that were isolated from the CSF of 45 healthy people between the ages of 54 and 83, and 14 adults with cognitive impairments, as determined with memory tests.
The researchers found that in older, healthy people, the immune cells from CSF expressed genes that indicated that they were more activated and inflamed. "The immune cells appear to be a little angry in older individuals," .. and that may cause these cells to lose functionality, and dysregulation in the immune system in the brain, Gate said.
The immune cells from people with cognitive impairments were disrupted as well; T cells were inflamed, and reproducing more of themselves. They flowed into the brain like a radio signal, Gates added. These cells expressed high levels of a receptor called CXCR6, which interacts with CXCL16, a molecule made by degenerating microglia cells, to allow more dysfunctional T 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 researchers would like to know more about how to block or inhibit this signal, and whether that has an effect on neurodegeneration, such as what is seen in Alzheimers or other brain diseases.
Sources: Northwestern University, Cell
