Acta Neuropathologica

, Volume 117, Issue 5, pp 583–589 | Cite as

Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis

  • Jane Marian Anderson
  • Rickie Patani
  • Richard Reynolds
  • Richard Nicholas
  • Alastair Compston
  • Maria Grazia Spillantini
  • Siddharthan Chandran
Case Report
First Online:
Received:
Revised:
Accepted:

Abstract

Although progression in multiple sclerosis is pathologically dominated by neurodegeneration, the underlying mechanism is unknown. Abnormal hyperphosphorylation of tau is implicated in the aetiopathogenesis of some common neurodegenerative disorders. We recently demonstrated the association of insoluble tau with established secondary progressive MS, raising the hypothesis that its accumulation is relevant to disease progression. In order to begin to determine the temporal emergence of abnormal tau with disease progression in MS, we examined tau phosphorylation in cerebral tissue from a rare case of early aggressive MS. We report tau hyperphosphorylation occurring in multiple cell types, with biochemical analysis confirming restriction to the soluble fraction. The absence of sarcosyl-insoluble tau fraction in early disease and its presence in secondary progression raises the possibility that insoluble tau accumulates with disease progression.

Keywords

Tau Acute inflammatory demyelinating disease Experimental autoimmune encephalomyelitis Axonopathy Neuronal loss 

Abbreviations

CNS

Central nervous system

LFB

Luxol fast blue

mAb

Monoclonal antibody

NGS

Normal goat serum

PB

Phosphate buffer

PBS

Phosphate buffered saline

TX-PBS

Triton-phosphate buffered saline

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Notes

Acknowledgments

These studies were supported by the Webb Trust Fund, Husky Foundation, the Sir David Walker Trust Fund, the Medical Research Council, Wellcome Trust and MS Society of Great Britain and Northern Ireland and the National Multiple Sclerosis Society, USA. Tissue samples were supplied by the UK MS Tissue Bank, funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland, registered charity 207495.

Conflict of interest statement

The authors report no conflicts of interest.

Supplementary material

401_2009_515_MOESM1_ESM.tif (1.5 mb)
Immunohistochemical and histological characterisation of control fronto-parietal tissue with no known neuropathological disease. Normal myelin staining (LFB) of a white matter tract flanked by grey matter is shown. Inset demonstrates a representative high powered image of microglia immunolabelled with HLA-DR/LN-3, which sparsely populate healthy cerebral tissue. The resting ramified state shown is in contrast to the amoeboid morphology seen in active multiple sclerosis lesions (Fig 1c). Scale bars: main image:1mm; inset: 50μm. (TIFF 1504 kb)

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jane Marian Anderson
    • 1
  • Rickie Patani
    • 1
  • Richard Reynolds
    • 2
  • Richard Nicholas
    • 2
  • Alastair Compston
    • 1
  • Maria Grazia Spillantini
    • 1
  • Siddharthan Chandran
    • 1
  1. 1.Cambridge Centre for Brain Repair, Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK
  2. 2.Department of Cellular and Molecular NeuroscienceImperial College Faculty of Medicine, Charing Cross Hospital CampusLondonUK

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