NEURONAL APOPTOSIS IN FATAL FAMILIAL INSOMNIA

The possibility that neuronal loss in prion diseases occurs through an apoptotic process has been postulated and is consistent with the lack of inflammation in these disorders. In order to test this hypothesis in FFI, in which neuronal loss is the predominant neuropathological fe ature, we examined samples of thalamus, basal ganglia, cerebral cortex , cerebellum and medulla from 10 subjects with FR. All the patients ha d the characteristic 178 N mutation of the PrP gene. Eight subjects we re homozygous methionine/melhionine at codon 129 and 2 were heterozygo us methionine/valine. Apoptotic neurons were identified by in site end labelling in all the FFI cases and in none of the controls, They were mostly found in damaged regions and their presence and abundance seem ed to correlate closely with the neuronal loss, They were particularly abundant in the thalamus and medullary olives, In heterozygous cases who had a longer disease duration and more widespread cerebral changes , apoptotic neurons were also found in the neocortex and striatum. The abundance of apoptotic neurons also correlated well with microglial a ctivation as demonstrated by the expression of major histocompatibilit y complex class II antigens, PrPres immunostaining was almost invariab ly negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrPres deposits in prion diseas es.