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

Cytosolic phospholipase A1 alpha (cPLA2 alpha) 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 cPLA2 alpha knockout mice, three lines of APP/PS1 Tg-AD mice were produced with genotypes of cPLA2 alpha(+/+), cPLA2 alpha(+/-) and cPLA2 alpha(-/-). Compared to cPLA2 alpha(+/+) Tg-AD mice; the amyloid plaque formation was significantly downregulated in the brain of cPLA2c alpha(+/+) Tg-AD mice, but not in cPLA2 alpha(-/-) TgAD mice. The reactive gliosis were also significantly downregulated in both cPLA2 alpha(-/-) and cPLA2 alpha(+/+) TgAD mouse lines. The paradoxical effects of cPLA2 alpha, on the amyloid plaques reveal a complex role of cPLA2 alpha alpha, in pathogenesis of AD and could be a potential target for prevention and treatment of AD. Published by Elsevier B.V.