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Metabolic Evidence for Cerebral Neurodegeneration in Spinocerebellar Ataxia Type 1

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Abstract

Autosomal-dominant spinocerebellar ataxia type 1 (SCA1) is an adult-onset progressive disorder with well-characterized neurodegeneration in the cerebellum and brainstem. The objective of this study is to evaluate neurochemical changes associated with neurodegeneration in cerebral tissue in SCA1 patients compared to age- and gender-matched healthy controls. Nine patients with genetically proven SCA1 and nine gender- and age-matched healthy controls were prospectively recruited from the ataxia clinic and received clinical examination. A 1.5 T single-voxel brain proton MR spectroscopy was performed for total N-acetyl aspartate (tNAA) in cerebellum, parietofrontal lobe white matter, sensory cortex, and visual cortex. In the patients, tNAA was severely decreased in the cerebellar voxel; however, in the voxels positioned in sensory cortex, parietofrontal lobe white matter and visual cortex tNAA was reduced in comparison to controls. In addition to the profoundly affected cerebellum, we also found evidence for cerebral neurodegeneration in parietal lobe white matter, sensory cortex, and visual cortex in SCA1 patients illustrating a multisystem neurodegenerative character of the disease.

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG Exc. 257).

Conflicts of interest

Sarah Stricker, Alexander U Brandt, Timm Oberwahrenbrock and Jan Leo Rinnenthal report no conflict of interest. Friedemann Paul reports to have received grant support from Sanofi, Beyer, Pfizer, and Teva where he sees no direct conflict of interest with this work. Matthias Endres has no direct conflict of interests concerning this manuscript. He has received grant support from AstraZeneca and Sanofi, has participated in advisory board meetings of Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Pfizer, Sanofi and has received honoraria from Astra Zeneca, Bayer, Berlin Chemie, Bristol-Myers Squibb, Boehringer-Ingelheim, Desitin, Eisei, Ever, Glaxo Smith Kline, MSD, Novartis, Pfizer, Sanofi, Takeda, Trommsdorff.

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Authors and Affiliations

  1. Department of Neurology, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Sarah Doss & Matthias Endres

  2. Excellence Cluster NeuroCure, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Sarah Doss, Alexander U. Brandt, Timm Oberwahrenbrock, Matthias Endres & Friedemann Paul

  3. Max-Delbrück Center for Molecular Medicine Berlin, Lindenberger Weg 80, 13125, Berlin, Germany

    Sarah Doss

  4. Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Friedemann Paul

  5. Department of Neuropathology, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Jan Leo Rinnenthal

  6. Centrum für Schlaganfallforschung Berlin (CSB), Charité – Universitätsmedizin Berlin, Berlin, Germany

    Matthias Endres

Authors
  1. Sarah Doss
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  2. Alexander U. Brandt
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  3. Timm Oberwahrenbrock
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  4. Matthias Endres
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  5. Friedemann Paul
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  6. Jan Leo Rinnenthal
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Corresponding author

Correspondence to Sarah Doss.

Additional information

Friedemann Paul and Jan Leo Rinnenthal equally contributed to this study.

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Doss, S., Brandt, A.U., Oberwahrenbrock, T. et al. Metabolic Evidence for Cerebral Neurodegeneration in Spinocerebellar Ataxia Type 1. Cerebellum 13, 199–206 (2014). https://doi.org/10.1007/s12311-013-0527-2

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  • DOI: https://doi.org/10.1007/s12311-013-0527-2

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