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Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis

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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.

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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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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.

Author information

Authors and Affiliations

  1. Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK

    Jane Marian Anderson, Rickie Patani, Alastair Compston, Maria Grazia Spillantini & Siddharthan Chandran

  2. Department of Cellular and Molecular Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital Campus, Fulham Palace Road, London, UK

    Richard Reynolds & Richard Nicholas

Authors
  1. Jane Marian Anderson
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  2. Rickie Patani
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  3. Richard Reynolds
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  4. Richard Nicholas
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  5. Alastair Compston
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  6. Maria Grazia Spillantini
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  7. Siddharthan Chandran
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Corresponding author

Correspondence to Siddharthan Chandran.

Additional information

J. M. Anderson and R. Patani are co-first authors.

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401_2009_515_MOESM1_ESM.tif

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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Anderson, J.M., Patani, R., Reynolds, R. et al. Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis. Acta Neuropathol 117, 583–589 (2009). https://doi.org/10.1007/s00401-009-0515-2

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  • DOI: https://doi.org/10.1007/s00401-009-0515-2

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