Frontal lobe degeneration: novel ubiquitin-immunoreactive neurites within frontotemporal cortex

Ubiquitin-protein conjugates have been identified in filamentous inclusions in various neurodegenerative disorders. In frontal lobe degeneration (FLD) no distinctive histological features have been reported with the exception of some ubiquitin-positive intraneuronal inclusions in cases associated with motor neuron disease. In the present study, we investigated five FLD cases without motor neuron disease using immunohistochemistry. A constant feature in all cases consisted of ubiquitin-positive neurites in layers I-III of the frontotemporal neocortex. These neurites were not argyrophilic, and could not be labelled with various antibodies against tau and neurofilament proteins. Ubiquitin-protein conjugates were found in distended dendritic branches, in dendritic spines and in smooth slender neurites, probably axons. No ubiquitinated neurites were seen in corresponding areas of the brain in aged controls. The nature of ubiquitinated proteins in FLD and the reason why they are confined to nerve cell processes is unknown but may be understood as part of an ongoing process leading to cell death observed in FLD.