[P2–192]: EFFECT OF SET PHOSPHORYLATION ON ALZHEIMER's DISEASE

Inhibitor 2 of PP2A (I2 PP2A), also known as SET, is increased in AD brain. Casein kinase 2(CK2) is a serine/threonine protein kinase, which is also increased in AD and may involve in tau accumulation and SET phosphorylation. However, whether CK2 phosphorylating SET mediates the neurofibrillary pathology in AD remains unknown. The level of CK2 and its substrates weretested in different AD mice by Western blotting. CK2 activity was measured by using a CK2 activity assay kit. An adeno-associated virus serotype 2 (AAV2) was employed to induce expression of CK2in mice brain. Fear conditioning and Morris water maze were used to detect animal behavior. Synaptic function was measured by LTP and Golgi-Cox staining. Immunofluorescence was used to detect the location of phosphorylated SET.HEK293-Tauwere transfected with SET/wt, SET S9A and SET S9E plasmids for 48 hours. Cell lysates were collected for PP2A activity assay and Western blotting. CK2 overexpression induced tau pathology associated with cognitive defect and synaptic impairment. Meanwhile, CK2 phosphorylated SET at Ser9 and regulated SET nuclear import. However, mutation of SET Ser 9 to Ala abolished CK2-induced tau pathology in Alzheimer's disease. CK2-mediated phosphorylation of SET at Ser9 play an essential role in inducing tau pathology in Alzheimer's disease.