Journal article
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
P Lei, S Ayton, DI Finkelstein, L Spoerri, GD Ciccotosto, DK Wright, BXW Wong, PA Adlard, RA Cherny, LQ Lam, BR Roberts, I Volitakis, GF Egan, CA McLean, R Cappai, JA Duce, AI Bush
Nature Medicine | NATURE PORTFOLIO | Published : 2012
DOI: 10.1038/nm.2613
Abstract
The microtubule-associated protein tau has risk alleles for both Alzheimer's disease and Parkinson's disease and mutations that cause brain degenerative diseases termed tauopathies. Aggregated tau forms neurofibrillary tangles in these pathologies, but little is certain about the function of tau or its mode of involvement in pathogenesis. Neuronal iron accumulation has been observed pathologically in the cortex in Alzheimer's disease, the substantia nigra (SN) in Parkinson's disease and various brain regions in the tauopathies. Here we report that tau-knockout mice develop age-dependent brain atrophy, iron accumulation and SN neuronal loss, with concomitant cognitive deficits and parkinsonis..
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Funding Acknowledgements
This work was supported by funds from the Australian Research Council, the National Health & Medical Research Council of Australia (NHMRC) and the Alzheimer's Association. The Victorian Brain Bank Network is supported by The University of Melbourne, The Mental Health Research Institute, The Alfred Hospital and the Victorian Forensic Institute of Medicine, and funded by Neurosciences Australia and the NHMRC. The authors thank Y-H. Hung, H. Kim, S.H. Bush and A. Sedjahtera for helpful discussion and technical assistance, H.N. Dawson (Duke University) for providing the tau-knockout mice, and TA. Rouault and D.L. Zhang (US National Institutes of Health) for MAP23 antibody.