Since elevated mTORC1 in TS prevents autophagy-mediated clearance of pathogenic tau aggregates (Alquezar et al., 2021), early post-translational tau modifications may progressively lead to the accumulation of tau aggregates and early-onset dementia and neurodegeneration, especially since hyperphosphorylated tau promotes the self-assembly of tau neurofibrillary tangles (Iqbal et al., 2010). This evidence concerns the gene MAPT and Timothy syndrome.