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Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease

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Abstract

Mutations in the PARK7 gene DJ-1 are associated with recessive hereditary Parkinson’s disease (PD). Fibrillar inclusions of α-synuclein comprise the neuropathological hallmarks of PD and related Lewy body diseases as well as multiple system atrophy (MSA). Moreover, neuronal and glial inclusions containing tau have been observed in α-synucleinopathy patients. Using a collection of antibodies against DJ-1, we have performed a comprehensive investigation of DJ-1 in α-synucleinopathies and tauopathies. DJ-1 was abundantly expressed in reactive astrocytes of patients with neurodegenerative diseases. Likewise, DJ-1 antiserum immunostained reactive astrocytes that became abundant with disease progression in the brain stem of transgenic mice expressing mutant [A30P]α-synuclein. Human Lewy bodies as well as Lewy body-like inclusions in the α-synuclein transgenic mice were DJ-1 negative. Neuronal tau inclusions were DJ-1 immunopositive in Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease. In addition, we found DJ-1-immunopositive glial inclusions in CBD, PSP and MSA. Biochemical extraction experiments revealed the specific presence of insoluble, modified DJ-1 in PiD and MSA. Our results suggest that DJ-1 is up-regulated in reactive astrocytes as well as in neuronal and glial cells with specific α-synucleinopathy and tauopathy.

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Acknowledgements

We thank P. Rizzu and P. Heutink for the donation of antisera against DJ-1, I. Pigur and S. Odoy for technical assistance, and M. Farrer for helpful discussions. This work was supported by the German National Genome Research Network (NGFN), the (N)EUROPARK consortium funded by the European Community, and the Deutsche Forschungsgemeinschaft (Collaborative Research Center SFB596 and KFO 113/1). The German Brain Bank “Brain-Net” (http://www.brain-net.net) is supported by the German Federal Ministry of Education and Research.

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Authors and Affiliations

  1. Institute of Neuropathology, Ludwig Maximilians University of Munich, Munich, Germany

    Manuela Neumann & Hans A. Kretzschmar

  2. Laboratory of Alzheimer’s and Parkinson’s Disease Research, Department of Biochemistry, Ludwig Maximilians University of Munich, Schillerstrasse 44, 80336, Munich, Germany

    Veronika Müller, Karin Görner, Christian Haass & Philipp J. Kahle

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  1. Manuela Neumann
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Correspondence to Philipp J. Kahle.

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Neumann, M., Müller, V., Görner, K. et al. Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol 107, 489–496 (2004). https://doi.org/10.1007/s00401-004-0834-2

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  • DOI: https://doi.org/10.1007/s00401-004-0834-2

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