An enzyme found in the brain could help to preserve cognitive resilience with advancing age, according to research in mice, humans and cells¹.

Researchers found that high levels of the enzyme are linked to low levels of inflammation in the brains of aged mice. They also showed that the enzyme boosts the growth of neurons in ageing brains. The findings were reported on 15 October in Nature Neuroscience.

The enzyme seems to act “as a compensatory cognitive-resilience mechanism”, says study co-author Amar Sahay, a neuroscientist at Massachusetts General Hospital in Boston.

“This is a fantastic, very thoughtful approach to get at what could be protecting neurons,” says Timothy Hohman, a neuroscientist and geneticist at the Vanderbilt Memory & Alzheimer’s Center in Nashville, Tennessee, who was not involved in the study. “This is a great example of how you can use a model system to get at some of these resilience mechanisms that are super challenging to study in humans.”

A new neuroprotectant

The enzyme in question is a phospholipase, which breaks down fatty compounds. The authors homed in on the enzyme after finding that the gene encoding it suddenly became more active when connections between some of the neurons in the brains of mice were disrupted.

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To learn more, the scientists genetically altered mice to lack the gene, called Pla2g2f, and looked at what happened as they aged. The researchers saw a surge of inflammation and neuron degradation compared with the brains of unaltered control animals. By contrast, mice that had excess Pla2g2f displayed less inflammation and better-connected neurons in their brains as they got older.

The team also tested the animals’ spatial memory. These results, too, suggested that the enzyme provides protection. Young mice that were lacking Pla2g2f scored lower on the memory tests than did young control mice; older animals with boosted Pla2g2f scored higher on the test than did older control mice.

These findings show that Pla2g2f can be used to shift the trajectory of pathological ageing in mice, Sahay adds.

Human genetics

The gene might also have a protective role in humans. The authors analysed two large data sets^2,3 compiled by other scientists and found that PLA2G2F activity in the human brain rises with age.

Sahay collaborated with researchers who had collected gene-expression data⁴ from the brains of deceased human donors. The donors had all undergone cognitive testing before their death. Sahay’s team found that PLA2G2F activity was highest in ‘resilient’ individuals — people whose cognition remained intact even though their brains had deposits of a protein called amyloid-β. Such deposits are a feature of Alzheimer’s disease.

The brain cells linked to protection against dementia