A breakthrough discovery shows a potential cause of Alzheimer's disease

The research showed that the CSF immune system becomes dysregulated as people age. The study also discovered that the cerebrospinal fluid in patients with Alzheimer’s disease, and others with cognitive impairment, is significantly different from healthy individuals.

“We now have a glimpse into the brain’s immune system with healthy aging and neurodegeneration,” said David Gate, lead author of the study and assistant professor of neurology at Northwestern University Feinberg School of Medicine. “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.”

Gathering the data

The researchers provided a detailed analysis of the dysregulation of cerebrospinal fluid in healthy brains in comparison to brains with cognitive impairment. Gate and his team used single-cell RNA sequencing (scRNAseq) to evaluate the CSF.

Single-cell RNA sequencing was first described in 2009. The method requires isolating single cells and generating sequencing information, allowing for the assessment of specific properties of individual cells.

The study

The researchers from Northwestern University used scRNAseq to profile 59 CSF immune systems from various ages by taking the fluid from their spines and isolating the immune cells.

The study first looked at CSF in 45 healthy participants aged 54 to 83 years old. The second part of the study compared the CSF in 14 adults with cognitive impairment to the spinal fluid in the healthy adults.  The patients’ conditions were tested and determined by test results on memory exams, and the participants with cognitive impairment tested poorly.

Changes in the cells

The team noticed that there were genetic changes in the CSF immune cells in the older healthy participants, making the cells more activated with 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.”

The T-cells, or white blood cells of the immune system, that were inflamed cloned themselves and flowed into the CSF and brain, according to the study. Researchers discovered that the cells had an oversupply of a cell receptor called CXCR6.

The cell receptor acts as an antenna, receiving a signal, known as CXCL16, from the deteriorating brain’s microglia cells – the cells in the brain and spinal cord – 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 stated. “They do not belong there, and we are trying to understand whether they contribute to damage in the brain.”

The study was published today in the journal Cell.

The researchers want to continue exploring the role of immune cells in neurodegenerative diseases, like Alzheimer's. Gate said the "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.” 

Eventually, researchers could potentially be closer to a cure for Alzheimer’s disease, and other neurodegenerative diseases, by understanding the preliminary causes.