Proteomic Polygenic Risk Scores Of Age-Related Plasma Protein Levels Reveal A Role For Metalloproteinase Inhibitor 2 (Timp2) In Cognitive Performance

Genetically predicted higher levels of the plasma protein Metalloproteinase inhibitor 2 (TIMP2) are associated with better global cognition and memory performance in humans, consistent with its brain-rejuvenating role observed in mice.

Scientists have long observed that certain blood proteins can influence brain aging in animal models like mice, but applying these discoveries to human health has been a significant challenge. To bridge this gap, a new study explored the role of genetically predicted blood protein levels in human cognitive performance. Researchers first identified 12 proteins known to have aging or rejuvenating effects on mouse brains through a comprehensive review. They then developed “proteomic polygenic risk scores” (think of these as genetic indicators that estimate a person’s inherited tendency for higher or lower levels of specific proteins in their blood throughout life), validating their accuracy in two different groups of people. The key finding was that a higher genetic predisposition to elevated levels of a protein called Metalloproteinase inhibitor 2, or TIMP2, was significantly associated with better overall thinking abilities and memory in humans. This discovery reinforces earlier findings from mouse studies that suggested TIMP2 plays a role in brain rejuvenation. This alignment between animal and human data is crucial, as it suggests that TIMP2 could be a promising target for developing new treatments to combat brain aging and age-related conditions affecting the brain.