Research reportHeterozygous knockout of cytosolic phospholipase A2α attenuates Alzheimer's disease pathology in APP/PS1 transgenic mice

- Cytosolic phospholipase A2 alpha (cPLA2α) regulates integrity of the cell membrane and inflammation.
- Semi-knockout of cPLA2α in APP/PS1 transgenic mice reduces the plaque formation and gliosis.
- cPLA2α plays a complex role in AD pathogenesis.

Cytosolic phospholipase A2α (cPLA2α) is a key enzyme in regulation of inflammation process and neuromembrane homeostasis, both of which are critical in pathogenesis of Alzheimer's diseases. By hybride APP/PS1 Tg-AD mice with cPLA2α knockout mice, three lines of APP/PS1 Tg-AD mice were produced with genotypes of cPLA2α+/+, cPLA2α+/− and cPLA2α−/−. Compared to cPLA2α+/+ Tg-AD mice, the amyloid plaque formation was significantly downregulated in the brain of cPLA2α+/− Tg-AD mice, but not in cPLA2α−/− Tg-AD mice. The reactive gliosis were also significantly downregulated in both cPLA2α+/− and cPLA2α−/− Tg-AD mouse lines. The paradoxical effects of cPLA2α on the amyloid plaques reveal a complex role of cPLA2α in pathogenesis of AD and could be a potential target for prevention and treatment of AD.