JNPL3Hlmc transgenic mice treated with SRN-003-556 have reduced levels of soluble aggregated 64-kDa hyperphosphorylated tau species. Tau proteins were extracted from spinal cord tissue and analyzed by Western blotting with phosphospecific antibodies AP422, AT8, and anti-pS262, followed by normalization of the signals for exposure and expression/loading. (A) AP422 and AT8 antibodies detected only the 64-kDa tau species, whereas anti-pS262 also detected the normal tau species (≈55 kDa). Quantification of the blots revealed significantly lower levels of the pathological 64-kDa tau species in the treated group compared with the vehicle group by the criteria of normalized immunoreactivities with AP422 (B), AT8 (C), anti-pS262 (D), and HT7 (E). (F) Representative for all 64-kDa tau markers, AP422 signals correlated well with phenotypic stage (Spearman r, 0.8284; P < 0.0001).