To treat Alzheimer’s disease, researchers discovered immunological reservoir

The fluid that surrounds and flows throughout your brain and spinal cord, called cerebrospinal fluid (CSF), is what gives your three-pound brain the sensation of weightlessness. This liquid barrier that separates your brain from your skull and moisturises it protects it from head injuries.

The CSF also protects the brain’s immunological system, which is a crucial but lesser-known role. But little research has been done on this function. CSF’s function in conditions like Alzheimer’s disease that cause cognitive impairment has been uncovered by a Northwestern Medicine research. According to research main author David Gate, an associate professor of neurology at Northwestern University Feinberg School of Medicine, this finding offers a fresh insight into the process of neurodegeneration.

The research will appear in Cell. According to the study, as people age, their CSF immune system degenerates. The study also found that the CSF immune system is significantly different in patients with cognitive impairment, such as those with Alzheimer’s disease.

“We now have a glimpse into 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 be used as a diagnostic to determine the level of brain inflammation in individuals with dementia.” “We provide a thorough analysis of this important immunologic reservoir of the healthy and diseased brain,” Gate said. His team is sharing the data publicly, and its results can be searched online.

Gate’s team at Northwestern employed a cutting-edge method called single-cell RNA sequencing to examine the CSF. They extracted CSF from participants’ spines, isolated the immune cells within it, and then analysed 59 CSF immune systems across a range of ages. The CSF of 45 healthy people between the ages of 54 and 83 was examined in the study’s first section.

The CSF of 14 persons with cognitive impairment, as established by their low scores on memory tests, was compared to those results in the healthy group in the study’s second component. In older healthy individuals, the CSF immune cells were shown to have genetic alterations that caused the cells to seem more active and inflamed with advancing age.

“The immune cells appear to be a little angry in older individuals,” Gate said. “We think this anger might make these cells less functional, resulting in dysregulation of the brain’s immune system.”

In the group with cognitive impairment, inflammatory T-cells replicated and moved into the CSF and brain as though they were responding to a radio signal, according to Gate. The cells were revealed to have an excess of CXCR6, a cell receptor that serves as an antenna. The microglia cells in the ageing brain send a signal called CXCL16 to this receptor, allowing it 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.”
Gate said his “future goal is to block that radio signal, or to inhibit the antenna from receiving that signal from the brain. We want to know what happens when these immune cells are blocked from entering brains with neurodegeneration.”