Rosenthal fibres are based on the ubiquitination of glial filaments

Immunocytochemical localization of the cell stress-associated protein ubiquitin was performed on human lesions containing Rosenthal fibres. Ubiquitin was localized around the periphery of classical Rosenthal fibres but not in the amorphous central areas; the ubiquitin-positive regions corresponded to the immunocytochemical localization of glial fibrillary acidic protein (GFAP). Compact bundles of GFAP in glial processes without a non-staining core were also associated with ubiquitin, while loosely aggregated cellular GFAP was not. The relationship between compact bundles of GFAP and the amorphous osmiophilic central component of Rosenthal fibres has been uncertain. These data, however, show that the compact bundles of glial filaments are distinct from normal GFAP in being associated with ubiquitin. A role for ubiquitin in Rosenthal fibre formation is suggested. We propose that the term Rosenthal fibre be restricted to mean the hyaline amorphous core of these structures, while realizing that this is based on a wider abnormality of surrounding glial fibrillary acidic protein filaments.