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


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.


Tau Acute inflammatory demyelinating disease Experimental autoimmune encephalomyelitis Axonopathy Neuronal loss 



Central nervous system


Luxol fast blue


Monoclonal antibody


Normal goat serum


Phosphate buffer


Phosphate buffered saline


Triton-phosphate buffered saline

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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