An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience | Nature Neuroscience

The aging-upregulated secreted phospholipase gene Pla2g2f confers neuroprotection and cognitive resilience, according to work by Vicidomini and Sahay at Mass General Brigham/Harvard published in Nature Neuroscience. In mice, reducing its expression worsened synaptic loss, inflammation and memory impairment, while boosting it in middle-aged animals altered the memory-aging trajectory. Pla2g2f limits lipid droplet and cholesteryl ester accumulation in microglia, and was expressed at higher levels in hippocampi of cognitively resilient older donors with Alzheimer's pathology. The work is preclinical, in mice and human cells.