Knockdown experiments further revealed that reduced GSK3β-but not GSK3α-reproduced the suppressive effect on PLA2G4A.<h4>Conclusion</h4>Our study identified the GSK3β/NF-κB/PLA2G4A signaling axis as a novel therapeutic target in AD, and AS could inhibit this axis to mitigate Aβ pathology by promoting lysosomal degradation of Aβ. Here, NFKB1 is linked to Alzheimer disease.