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60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

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Tau and synuclein pathology in Hereditary Spastic Paraplegia SPG7

Meeting Abstract

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  • corresponding author presenting/speaker Dietmar Thal - University of Ulm, Pathology, Ulm, Germany
  • Stephan Züchner - University of Miami Miller School of Medicine, Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miami, United States
  • Claudia Schulte - University of Tübingen, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; University of Tübingen, German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
  • Ludger Schöls - University of Tübingen, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; University of Tübingen, German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
  • Rebecca Schüle - University of Miami Miller School of Medicine, Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miami, Germany; University of Tübingen, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; University of Tübingen, German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
  • Matthis Synofzik - University of Tübingen, Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; University of Tübingen, German Research Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP6

doi: 10.3205/15dgnn30, urn:nbn:de:0183-15dgnn307

Published: August 25, 2015

© 2015 Thal et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: SPG7 is one of the most frequent causes of autosomal recessive Hereditary Spastic Paraplegias and spastic ataxias. Ala510Val is the most common mutation, with a frequency of up to 1% in the general population. The exact pathology caused by SPG7 and, in particular, the Ala510Val mutation, remains to be ascertained.

Results: Here, we show subcortical τ-pathology in a homozygous Ala510Val SPG7 case with a unique distribution pattern distinct from that of other tauopathies. The subcortical τ-lesions exhibited 4-repeat (4rp) τ but no 3rp τ. This τ-pathology was unraveled in the basal ganglia, pons, midbrain, medulla oblongata, and the cerebellar dentate nucleus. Cortical neurofibrillary tangles (NFTs) were limited to the transentorhinal cortex, representing the pattern of Braak-NFT stage I. In addition to the τ-lesions, α-synuclein containing Lewy bodies (LBs) were observed in the brain stem and the cortex, compatible with a pattern of Braak LB-Disease stage 5. In line with the established mitochondrial defects caused by SPG7 mutations, mitochondria in the substantia nigra neurons exhibited ultrastructural christae alterations.

Conclusion: This case report indicates that pathology of SPG7 includes a unique pattern of widespread subcortical τ and α-synuclein changes. The distribution of pathology includes several brain regions, which had not been implicated in SPG7 disease so far.