P4‐237: OXIDATIVE STRESS INDUCES AMYLOID AND TAU ALZHEIMER'S BIOMARKERS AND THE COGNITIVE DECLINE OF ALZHEIMER'S DISEASE BY PRODUCTION OF HOMOCYSTEIC ACID

immunized with full-length TDP-43. mTDP-O antibodies were further characterized by dot blot, WB and ELISA assay. FTLD, ALS, and control tissue sections were stained with mTDP-O antibodies. The TDP-43 injection mouse model we used is 5 monthold C57/BL6 mice. The mice were bilaterally injected with TDP43, TDP-43 premixed with one mTDP-O antibody, buffer control or IgG control into hippocampus. The spatial learning and memory were determined by Morris Water Maze. Results:We have generated a panel of mTDP-O antibodies, and characterized the affinity of these TDP-O antibodies against TDP-43 oligomers and monomers. Using mTDP-O antibodies, we found TDP-43 oligomers are present not only in hippocampi of FTLD-TDP patients, but in the motor cortex and spinal cord of ALS patients. Besides, TDP-43 oligomers are partially colocalized with phosphorylated TDP-43 in hippocampus regions of FTLD-TDP patients. The results of Morris Water Maze test in the TDP-43 oligomer injection mouse model showed that TDP-43 oligomer injected mice was deficient in long-term memory. In contrast, the mice injected with TDP-43 oligomer premixed with the mTDP-O antibody behaved normally. The results indicated that the mTDP-O antibody can neutralize the toxicity effect of TDP-43 oligomers. Besides, since TDP-43 pathology presents in up to 57% of AD, now we are using mTDP-O antibodies to evaluate the prevalence of TDP-43 oligomers in AD tissues. Conclustions:TDP-43 oligomers exist in FTLD and ALS patients. Now we are studying whether TDP oligomers are present in AD brain tissues. Moreover, one mTDP-O antibody can neutralize TDP-43 oligomers induced toxicity. TDP-43 oligomer is a potential therapeutic target for TDP-43 pathology related diseases.