Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation

Int J Mol Sci. 2015 Oct 21;16(10):25050-66. doi: 10.3390/ijms161025050.


Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.

Keywords: Lewy bodies; SPG7; ataxia; coiled bodies; neurofibrillary tangles; paraplegin; spastic ataxia; spastic paraplegia; tau.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Aged
  • Basal Nucleus of Meynert / pathology
  • Cerebellar Nuclei / pathology
  • Gene Frequency / genetics
  • Gliosis / genetics
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Lewy Bodies / pathology
  • Male
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / genetics*
  • Muscle Spasticity / genetics*
  • Muscle Spasticity / pathology
  • Neurites / metabolism*
  • Neurofibrillary Tangles / pathology
  • Neurons / pathology
  • Olivary Nucleus / pathology
  • Optic Atrophy / genetics*
  • Optic Atrophy / pathology
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / pathology
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / pathology
  • Substantia Nigra / pathology
  • alpha-Synuclein / metabolism*
  • tau Proteins / metabolism*


  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins
  • Metalloendopeptidases
  • SPG7 protein, human
  • ATPases Associated with Diverse Cellular Activities

Supplementary concepts

  • Spastic Ataxia