Taken together, our results indicate that specific soluble tau PTMs are specifically associated with 3R-tau aggregates (Ac-K311, P-S184 + P-S185), 4R-tau aggregates (Ub-K343, Ub-K369), or AD-tau aggregates (Ub-K311, Ub-K317, Ub-K267 + P-S262), making these soluble tau PTMs potential candidates for tauopathy distinction in biological fluids. The gene discussed is MAPT; the disease is tauopathy.