We found that ASO-Ttbk1#1 significantly reduced pS396, one of the phosphor epitopes in paired helical filaments (PHF) in S1 (p = 0.0332), S2 (p = 0.0138) and P2 (p < 0.0001) fractions (Additional file 1: Fig. S1A, Fig. 3A, B), pT231in S2 (p = 0.0043) and P2 fractions (p = 0.0225) and pT181 tau in S2 fraction (p = 0.0246), both of which are early AD biomarkers in cerebrospinal fluid [11, 12, 23, 24], compared to ASO-control group (Fig. 3C–F). This evidence concerns the gene MAPT and Alzheimer disease.