This article from Nature Medicine detailing a large-scale proteomic study on the balance of proteins between cerebrospinal fluid (CSF) and plasma in relation to cognitive impairment and aging. Researchers used SomaScan proteomics on paired CSF and plasma samples from over 2,100 individuals to analyze CSF-to-plasma protein ratios, offering insight into brain barrier function. The findings reveal that CSF-to-plasma ratios for many proteins, particularly those from peripheral sources, increase with age, suggesting barrier dysfunction or reduced clearance. Additionally, the study identified sex differences in these ratios and found that lower ratios of certain peripherally derived proteins, like DCUN1D1, MFGE8, and VEGFA, are associated with worse cognitive function. Finally, genome-wide association studies (GWAS) identified genetic loci, such as those related to TCN2 and FCN2, that are linked to changes in these protein ratios, which may be crucial for therapeutic delivery to the brain.
References:
- Farinas A, Rutledge J, Bot V A, et al. Disruption of the cerebrospinal fluid-plasma protein balance in cognitive impairment and aging[J]. Nature Medicine, 2025: 1-12.
