Acta Neuropathologica

, Volume 121, Issue 4, pp 519–527

Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders

  • Tibor Hortobágyi
  • Claire Troakes
  • Agnes L. Nishimura
  • Caroline Vance
  • John C. van Swieten
  • Harro Seelaar
  • Andrew King
  • Safa Al-Sarraj
  • Boris Rogelj
  • Christopher E. Shaw
Original Paper

DOI: 10.1007/s00401-011-0813-3

Cite this article as:
Hortobágyi, T., Troakes, C., Nishimura, A.L. et al. Acta Neuropathol (2011) 121: 519. doi:10.1007/s00401-011-0813-3

Abstract

Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer’s disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington’s disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and α-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.

Keywords

Amyotrophic lateral sclerosis (ALS) Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) Immunohistochemistry Motor neurone disease (MND) Optineurin (OPTN) Western blotting 

Supplementary material

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tibor Hortobágyi
    • 1
  • Claire Troakes
    • 1
  • Agnes L. Nishimura
    • 1
  • Caroline Vance
    • 1
  • John C. van Swieten
    • 2
  • Harro Seelaar
    • 2
  • Andrew King
    • 3
  • Safa Al-Sarraj
    • 3
  • Boris Rogelj
    • 1
  • Christopher E. Shaw
    • 1
  1. 1.Department of Clinical NeuroscienceKing’s College London, MRC Centre for Neurodegeneration Research, Institute of PsychiatryLondonUK
  2. 2.Department of NeurologyErasmus University Medical Center RotterdamRotterdamThe Netherlands
  3. 3.Department of Clinical NeuropathologyKing’s College HospitalLondonUK

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