Recently, multiple efforts are being made to reduce the tau accumulation in AD, by using such as tau antisense oligonucleotides,3 antibodies,4 PROteolysis TArgeting Chimeras (PROTACs),5,6 and the structure-based tau aggregation inhibitors.7,8 It is well known that tau hyperphosphorylation initiates the abnormal tau aggregation and induces neurodegeneration in the brains of AD and the related tauopathies,9 however, there is currently no strategy for specifically targeting tau phosphorylation at the post-translational level. The gene discussed is MAPT; the disease is Alzheimer disease.