These and other data indicate that: (a) chaperones not only alleviate but also aggravate Tau aggregation, and hence identification and analysis of chaperones that modulate Tau-aggregation and toxicity are required to understand biological and pathogenic mechanisms involved in Tauopathy, and (b) genetic or pharmacological manipulation of specific chaperone activities could be of possible therapeutic value for treating Tau-induced neurodegeneration. The gene discussed is MAPT; the disease is tauopathy.