DC8E8 immunotherapy significantly reduces levels of insoluble tau oligomers in brains of transgenic mice. Tau transgenic mice were immunized with DC8E8 and with an irrelevant antibody, DC51, and brain tissue of the animals was fractionated into soluble and sarcosyl-insoluble tau fractions. (A) and (B) Amount of total soluble tau is unchanged after DC8E8 treatment compared with treatment with a mock antibody, DC51. (C) and (D) Amount of sarcosyl-insoluble tau oligomers in transgenic mouse brain is significantly diminished after treatment with DC8E8 (n = 3, **P < 0.01). All Western blots were stained with pan-tau monoclonal antibody DC25, and lanes 1 to 6 contain samples from individual animals used in the experiments. Signal quantification was performed using AIDA software.