Neuronal apoptosis in Creutzfeldt-Jakob disease

Neuronal loss is a salient feature of prion diseases; however, its causes a nd mechanisms are unclear. The possibility that it could occur through an a poptotic process has been postulated and is consistent with the lack of inf lammation in prion disorders as supported by experimental studies. In order to rest this hypothesis in humans, we examined samples of frontal and temp oral cerebral cortex, striatum, thalamus, and cerebellum from 16 patients w ho died from Creutzfeldt-Jakob disease. They included 5 sporadic cases, 5 f amilial, 3 iatrogenic, and 3 cases with the new variant. These were compare d with age and sex matched controls. Using in situ end labelling, we identi fied apoptotic neurons in all the cases of Creutzfeldt-Jakob disease. A sin gle labelled neuron was found in the eldest control. Apoptotic neurons were mostly found in damaged regions and their presence and abundance seemed to correlate closely with neuronal loss. This supports the view that apoptosi s of neurons is a feature of prion diseases and may contribute to the neuro nal loss which is one of the main characteristics of these conditions. Neur onal apoptosis also correlated well with microglial activation, as demonstr ated by the expression of major histocompatibility complex class II antigen s, and axonal damage, as identified by beta-amyloid protein precursor immun ostaining. In contrast, we found no obvious relationship between the topogr aphy and severity of neuronal apoptosis and the type, topography, and abund ance of prion protein deposits as demonstrated by immunocytochemistry.