Brain Enzyme Study Links High Pla2g2f Levels to Cognitive Resilience in Aging
High levels of a newly identified brain enzyme help preserve cognitive resilience and lower inflammation as the brain ages, according to research published on October 15 in Nature Neuroscience. Investigators discovered that the enzyme, known as a phospholipase encoded by the gene Pla2g2f, breaks down fatty compounds and increases in activity as the brain experiences synapse loss and inflammation.
How Genetic Alterations in Mice Reveal Neuroprotection
To understand the function of the enzyme, scientists genetically altered mice to lack the Pla2g2f gene. These mice experienced a surge of brain inflammation and neuron degradation as they aged, compared to unaltered control animals. Middle-aged mice lacking the gene also scored lower on spatial memory tests than control mice of the same age.
Conversely, mice engineered to have excess Pla2g2f displayed less brain inflammation and better-connected neurons over time. Older animals with boosted enzyme levels scored higher on spatial memory tests than older control animals. According to study co-author Amar Sahay, the findings show that the enzyme acts as a compensatory cognitive-resilience mechanism that can shift the trajectory of pathological aging in mice.
Human Brain Data Show Higher Enzyme Activity in Resilient Donors
Analysis of human tissue data indicates that the gene may also play a protective role in humans. Sahay collaborated with researchers who analyzed gene-expression data from the brains of deceased human donors who had undergone cognitive testing before death. The analysis revealed that PLA2G2F activity in the human brain rises with age and is highest in resilient individuals whose cognition remained intact despite brain deposits of amyloid-β protein, a hallmark of Alzheimer’s disease.
Before this study, the specific role of the Pla2g2f-produced phospholipase in the brain was unknown. Cinzia Vicidomini and Amar Sahay led the research team behind the published paper.
Therapeutic Exploration and Future Research Steps
Aging remains the greatest risk factor for Alzheimer’s disease, and researchers are actively exploring ways to safely increase Pla2g2f levels in the aging brain as a potential therapeutic strategy. Additional studies will be required to determine whether boosting this enzyme can be safely translated into treatments for patients to delay or prevent mild cognitive impairment and Alzheimer’s disease.
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