This study shows that mice lacking tau protein develop Parkinsonism because of intracellular iron accumulation which in turn causes degeneration of dopamine neurons. Tau deficiency appears to impair ferroportin iron export from cells by retention of the amyloid precursor protein. Amyloid precursor protein is a neuronal ferroxidase partner inside the endoplasmic reticulum. Tau-knockout mice developed age-dependent brain atrophy, iron accumulation and substantia nigra neuronal loss, as well as cognitive deficits and parkinsonism. These changes were prevented by oral treatment with the iron chelator, clioquinol. These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer’s disease, Parkinson’s disease and tauopathies, and that it can be rescued pharmacologically.
Lei P, Ayton S, Finkelstein DI, Spoerri L, et al.: Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nature Medicine 18, 291–295 (2012).
