The Cerebrospinal Fluid (CSF) Immune System Shows Differences in Individuals with Cognitive Impairment

• A study published in Cell found that as people age, their CSF immune system becomes dysregulated.  
• The researchers noted that older individuals experienced genetic changes. These made CSF immune cells more activated and inflamed than their younger counterparts.  
• CXCL16 increases cognitively impaired CSF and relates to neurodegeneration.  

The cerebrospinal fluid (CSF) immune system shows key differences between individuals with cognitive impairment and those with normally functioning brains. This is the key finding of a Northwestern Medicine study published in Cell.   

The investigators performed single/cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54 to 82 years old. To che results proved an upregulation of lipid transport genes in monocytes with age. Basically, the study adds valuable information about how CSF immunity is altered with aging or neurodegenerative disease.  

As a result, the researchers noted that older individuals experienced genetic changes that made CSF immune cells more activated and inflamed than their younger counterparts. Additionally, the study found that their CSF immune system becomes dysregulated as people age. In people with cognitive impairment, such as those with Alzheimer’s disease, the CSF immune system is drastically different from healthy individuals.

Therefore, the major highlights of this Cerebrospinal fluid research are: 

• Monocytes upregulate lipid processing genes with age in cognitively normal CSF.  
• Monocyte lipid processing genes dysregulate in cognitively impaired CSF.  
• Monocytes signal to clonal CD8+ T cells via CXCL16-CXCR6 in cognitively impaired CSF.  
• CXCL16 is increased in cognitively impaired CSF and relates to neurodegeneration.  

According to the study’s lead author, David Gate, Ph.D., the immune cells appear to be a little angry in older individuals. “We think this anger might make these cells less functional, resulting in dysregulation of the brain’s immune system.”  

In the study, researchers of 14 participants with cognitive impairment—as determined by poor scores on memory tests—discovered the existence of inflamed T-cells with an overabundance of CXCR6 receptors cloning themselves and flowing into the CSF and the brain.    

Even if the CSF is commonly known for brain protection against physical injuries, these findings also highlight the importance of the surrounding fluid of the brain to provide an immune defense.   

“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,” Gate said.  

Read the complete study here Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment: Cell.  

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