The aim of this paper was to provide a comprehensive review of tau-directed drugs for the treatment of AD, with a particular focus on TAIs and the most clinically advanced of these compounds, that is, leucomethylthioninium (LMT, leucomethylene blue (MB), LMTXTM, TRx0237, TauRx Therapeutics Ltd., Republic of Singapore), a second-generation TAI for the AD treatment. This evidence concerns the gene MAPT and Alzheimer disease.