What this means
Mice that made more of this protein kept better memory as they aged. Mice without it showed more brain damage and memory loss.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Mice, plus human brain cells in a dish and a human study linking the protein to cognitive resilience
- Kind of research
- A study
The science
- Original title
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.
- Authors
- Vicidomini C, Goode TD, Yu R et al.
- Journal
- Nature neuroscience
- Published
- Oct 15, 2026
- Study type
- Study
- PMID
- 42881225 ↗
Abstract
Cognitive reserve theory posits that compensatory mechanisms during aging stave off cognitive decline and lower risk for Alzheimer's disease. Here, in a screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors in mice, we identified a secreted phospholipase, Pla2g2f, whose expression increases in DGCs during aging and is associated with cognitive resilience in humans. Pla2g2f deletion in DGCs exacerbates aging-associated pathophysiological changes, including synapse loss, inflammatory microglia, reactive astrogliosis, impaired neurogenesis, lipid dysregulation, lipid droplet accumulation and hippocampal-dependent memory loss. Conversely, boosting Pla2g2f in DGCs during aging is sufficient to prevent these pathophysiological alterations in hippocampal-cortical circuits, protect memory and prophylactically modify trajectory of cognitive decline. Mutagenesis of the catalytic site of PLA2G2F prevented lipid droplet mobilization and reduction of reactive gliosis and inflammatory microglia. Neuronal PLA2G2F mediates intercellular signaling to decrease lipid droplet and cholesterol ester load in human induced pluripotent stem cell-derived microglia. Our findings implicate PLA2G2F as a compensatory neuroprotective broadcast signal that maintains lipid homeostasis to counteract aging-associated cognitive decline.
Vicidomini C, Goode TD, Yu R et al. An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience. Nature neuroscience. 2026. doi:10.1038/s41593-026-02465-z. PMID: 42881225. https://pubmed.ncbi.nlm.nih.gov/42881225/