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Sporadic four-repeat tauopathy with frontotemporal degeneration, parkinsonism and motor neuron disease

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Abstract

We report a sporadic tauopathy of 6-year duration in a 76-year-old woman. Her initial symptoms were asymmetrical parkinsonism and muscle weakness, with apraxia appearing 2 years later. The brain showed frontal and temporal cerebral atrophy; severe neuronal loss and gliosis were observed in the precentral cortex (loss of Betz cells was also evident) and premotor area, and in the medial temporal lobe, including the temporal tip, amygdala, and hippocampal CA1-subiculum border zone. The substantia nigra showed moderate neuronal loss and gliosis. In the spinal cord, loss of the anterior horn cells and degeneration of the corticospinal tracts were a characteristic feature. In addition, in the affected regions, the remaining neurons were often found to contain intracytoplasmic inclusions resembling neurofibrillary tangles. Tau immunostaining revealed widespread glial-predominant lesions in the cerebral gray and white matter. In contrast, predominance of neuronal lesions (pretangles/tangles) was a feature in the subcortical gray matter, including the spinal cord. The remaining upper and lower motor neurons were also affected by tau pathology. Accumulated tau in these glial cells and neurons was clearly recognized by a specific antibody against four-repeat (4R) tau. The ultrastructural presence of tau-positive tubular structures was confirmed in the glial cells and neurons (tangles). Immunoblotting of a frozen frontal lobe sample revealed accumulation of 4R-predominant tau isoforms. No mutations were found in the tau gene. These findings indicate that a sporadic 4R tauopathy can cause frontotemporal degeneration, parkinsonism, and motor neuron disease. The present case could represent a new clinicopathological phenotype of non-familial tauopathy.

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Acknowledgements

We thank C. Tanda, J. Takasaki, Y. Ota, N. Kaneko and S. Egawa for their technical assistance. This work was supported by a grant from the Research Committee on Neurodegenerative Diseases, Ministry of Health, Labor and Welfare, Japan (H.T.), and a grant from the Reta Lila Weston Trust for Medical Research, UK (R.de S.).

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Author notes

  1. Yue-Shan Piao

    Present address: Department of Neuropathology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang Chun Street, 100053, Beijing, PR China

Authors and Affiliations

  1. Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, 951-8585, Niigata, Japan

    Yue-Shan Piao, Chun-Feng Tan & Hitoshi Takahashi

  2. Section of Neurology, Nagasaki Kita Hospital, 5-4-61 Nameshi, 852-8061, Nagasaki, Japan

    Keisuke Iwanaga & Mitsuhiro Tsujihata

  3. Department of Pathological Neuroscience, Resource Branch for Brain Disease Research CBBR, Brain Research Institute, University of Niigata, 951-8585, Niigata, Japan

    Akiyoshi Kakita

  4. Department of Neurology, Brain Research Institute, University of Niigata, 951-8585, Niigata, Japan

    Hiroki Takano & Masatoyo Nishizawa

  5. Queen Square Brain Bank, Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

    Tammaryn Lashley & Tamas Revesz

  6. Reta Lila Weston Institute of Neurological Studies, University College London, 46 Cleveland Street, London, W1T 4JF, UK

    Andrew Lees & Rohan de Silva

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  1. Yue-Shan Piao
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  2. Chun-Feng Tan
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  10. Rohan de Silva
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  11. Mitsuhiro Tsujihata
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Corresponding author

Correspondence to Hitoshi Takahashi.

Additional information

Y.-S. Piao and C.-F. Tan contributed equally to this work.

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Piao, YS., Tan, CF., Iwanaga, K. et al. Sporadic four-repeat tauopathy with frontotemporal degeneration, parkinsonism and motor neuron disease. Acta Neuropathol 110, 600–609 (2005). https://doi.org/10.1007/s00401-005-1086-5

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  • DOI: https://doi.org/10.1007/s00401-005-1086-5

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