Immunophilin FKBP52 induces Tau-P301L filamentous assembly in vitro and modulates its activity in a model of tauopathy

Growing evidence underlines the role attributed to abnormal forms of Tau in several neurodegenerative diseases known as tauopathies, including Alzheimer’s disease, which are characterized by accumulation of oligomers and filamentous Tau inclusions in the CNS. We identify a direct interaction of the immunophilin FK506-binding protein with a molecular mass of ∼52 kDa (FKBP52) and the pathological mutant of Tau containing a proline-to-leucine mutation at position 301 (Tau-P301L), inducing Tau-P301L oligomerization and assembly into filaments. This interaction has a considerable impact on the progress of the tauopathy because some early aspects of the disease are rescued, in vivo, by knocking down FKBP52. Our results open a new field for the study of FKBP52 pathophysiology in tauopathic dementias, including prediction of disease phenotype and search for new types of antipathological Tau treatments.