Neuronal loss is a salient feature of
prion diseases; however, its causes and mechanisms are unclear. The possibility that it could occur through an apoptotic process has been postulated and this is consistent with the lack of
inflammation in
prion disorders as supported by experimental studies. In order to test this hypothesis in humans, we examined samples of frontal and temporal cerebral cortex, striatum, thalamus and cerebellum from 26 patients who died from
prion diseases. They included 16 cases of
Creutzfeldt-Jakob disease (5 sporadic cases, 5 familial, 3 iatrogenic, and 3 cases with the new variant), and 10 cases of
fatal familial insomnia including 8 homozygotes
methionine/methionone at
codon 129 of the
prion protein gene and 2 heterozygotes. These were compared with age and sex matched controls. Using in situ end labelling, we identified apoptotic neurons in all the cases of
Creutzfeldt-Jakob disease. A single 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 apoptosis of neurons is a feature of
prion diseases and may contribute to the neuronal loss which is one of the main characteristics of these conditions. Neuronal apoptosis also correlated well with microglial activation as demonstrated by the expression of major histocompatibility complex
class II antigens and axonal damage as identified by
beta-amyloid protein precursor immunostaining. In contrast, we found no obvious relationship between the topography and severity of neuronal apoptosis and the type, topography and abundance of
prion protein deposits as demonstrated by immunohistochemistry.