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The proposed mechanism by which TDP-43 regulates tau expression. TDP-43 acts on intron 9 and promotes tau exon 10 inclusion in physiological condition. In the disease condition, truncations or mutations lead to its cytoplasmic aggregation and nuclear depletion. Loss of function of TDP-43 (as a result of the nuclear depletion) leads to suppression of tau exon 10 inclusion and 4R-tau expression, which consequently may contribute to the neurofibrillary pathology.
