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Open Access Research

Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases

Lilla Reiniger1, Ilaria Mirabile1, Ana Lukic23, Jonathan DF Wadsworth4, Jacqueline M Linehan4, Michael Groves1, Jessica Lowe4, Ronald Druyeh4, Peter Rudge34, John Collinge234, Simon Mead34 and Sebastian Brandner12*

Author Affiliations

1 Division of Neuropathology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

2 Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK

3 National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

4 MRC Prion Unit, UCL Institute of Neurology, London, UK

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Acta Neuropathologica Communications 2013, 1:8  doi:10.1186/2051-5960-1-8

Published: 9 May 2013

Abstract

Background

Sporadic, inherited and acquired prion diseases show distinct histological patterns of abnormal prion protein (PrP) deposits. Many of the inherited prion diseases show striking histological patterns, which often associate with specific mutations. Most reports have focused on the pattern of PrP deposition in the cortical or cerebellar grey matter.

Results

We observed that the subcortical white matter in inherited prion diseases frequently contained filamentous depositions of abnormal PrP, and we have analysed by immunohistochemistry, immunofluorescence and electron microscopy 35 cases of inherited prion disease seen at the UK National Prion Clinic. We report here that filamentous PrP is abundantly deposited in myelinated fibres in inherited prion diseases, in particular in those with N-terminal mutations.

Conclusions

It is possible that the presence of filamentous PrP is related to the pathogenesis of inherited forms, which is different from those sporadic and acquired forms.

Keywords:
Creutzfeldt-Jakob disease; Inherited prion disease; White matter; PRNP gene mutation; Octapeptide repeat insert mutation; OPRI; Gerstmann Sträussler Scheinker Syndrome; GSS; Transgenic mice; Axons; Myelin basic protein