A notion of possible contribution of tau “toxic gain of function” as the basic pathogenic underpinning of tauopathies was challenged after a study by SantaCruz et al. (123) who showed that switching off the abnormal expression of tau in a transgenic tauopathy mouse model stopped the neurodegeneration process and improved the cognitive function despite continued deposition of NFTs (124). This evidence concerns the gene MAPT and tauopathy.