Longevity & AgingBlood-Brain Barrier Protein Imbalance Mapped Across 2,171 Aging Brains
Researchers analyzed paired cerebrospinal fluid (CSF) and plasma samples from 2,171 older adults using SomaScan proteomics. They found that CSF-to-plasma ratios of 848 proteins—including complement, coagulation, and neurodegeneration-linked proteins—rise with healthy aging, while 64 ratios decline. Elevated ratios of peripherally derived proteins like VEGFA and MFGE8 correlated with preserved cognition. Genome-wide association studies pinpointed genetic variants controlling these ratios for 241 proteins, including FCN2, whose collagen-like domain may facilitate blood-CSF transport. The findings illuminate how brain barriers regulate protein exchange, how this regulation changes with age and disease, and may guide the design of brain-permeable therapeutics.
