Brain enzyme Pla2g2f linked to cognitive resilience in ageing, Nature Neuroscience study finds

16 October 2026

Research in mice, humans and cells has linked a brain enzyme to the preservation of cognitive resilience with advancing age. The findings were reported on 15 October in Nature Neuroscience. The enzyme is a phospholipase, which breaks down fatty compounds, and the gene encoding it is called Pla2g2f. Researchers found that high levels of the enzyme are linked to low levels of inflammation in the brains of aged mice, and that the enzyme boosts the growth of neurons in ageing brains. Mice genetically altered to lack the gene showed a surge of inflammation and neuron degradation as they aged compared with unaltered controls, while mice with excess Pla2g2f displayed less inflammation and better-connected neurons as they got older. Middle-aged mice lacking Pla2g2f scored lower on spatial memory tests than middle-aged controls, and older animals with boosted Pla2g2f scored higher than older controls. In humans, analysis of two large data sets found that PLA2G2F activity in the brain rises with age, and gene-expression data from the brains of deceased donors who had undergone cognitive testing showed that PLA2G2F activity was highest in resilient individuals, whose cognition remained intact even though their brains had deposits of amyloid-beta, a feature of Alzheimer's disease. Study co-author Amar Sahay, a neuroscientist at Massachusetts General Hospital in Boston, said the enzyme seems to act as a compensatory cognitive-resilience mechanism.