Tubulovesicular structures are consistently found in prion diseases including vCJD and FFI

Abstract

Tubulovesicular structures (TVS) are the only disease-specific structures found by electron microscopy in naturally occurring and experimentally induced prion diseases or transmissible spongiform encephalopathies (TSEs)1–2, 4–5. We reported here the largest series of brain biopsy specimens of Creutzfeldt-Jakob disease (CJD), variant CJD and fatal familial insomnia (FFI) studied by thin-section electron microscopy. Our material includes two series of brain biopsies. The first, comprising 9 biopsy specimens collected at the Laboratoire de R. Escourolle, Hopital de la Salpetriere, Paris, France were coded by one of us (J-J.H) and examined blindly. This series has been completed between 1982 and 1986 as a part of epidemiology study of CJD in France. The second series consisted of brain (right prefrontal cortex) biopsies obtained between 1995–1999 by open surgery from 1 FFI case in a new French family, 1 vCJD case, 9 cases of sporadic CJD, and 2 cases of iatrogenic (human growth hormone) CJD. TVS were found in all specimens including cases of FFI and vCJD. They appeared as spheres approximately 30 nm in diameter or short tubules of helical appearance. They were of higher electron density than synaptic vesicles; occasionally they clustered as paracrystalline arrays. Their composition is unknown but they are not composed of PrP3. Their constant presence in all TSEs studied so far, strongly suggests thair role in pathogenesis of these diseases. This study is supported by EC Neuro-Prion Network of Excellence.