Artikel
Tau and synuclein pathology in Hereditary Spastic Paraplegia SPG7
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Veröffentlicht: | 25. August 2015 |
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Gliederung
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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.