Figure 9.

TOMA forms complexes with tau oligomers. A, B, Quantitative analyses of tau oligomers as free or in complex with TOMA assessed using ELISA. Serum samples from P301L mice immunized either with TOMA or nonspecific IgG antibody were passed through a protein-A column. Tau oligomers and total tau in flow-through (“free” tau oligomers that did not form complex with the antibody) and the eluted fraction (antibodies and TOMA-oligomer complexes) were measured by ELISA. Quantitation of tau oligomers (A) and total tau (B) in the eluted fraction were higher compared with flow-through “free oligomers” as measured by T22 and HT7, respectively. ★★★★p < 0.0001; ★★★p < 0.001, two-way ANOVA, Bonferroni post hoc comparison. Most of the tau oligomers are complexed with TOMA. C, Schematic representation of the proposed mechanism of action for intravenously injected TOMA, which specifically modulates tau oligomers. A fraction of the injected TOMA crosses the BBB and binds extracellular oligomeric tau and tau oligomer levels in the serum peak at 1 h after injection.