Open AccessNeuronal Apoptosis in Fatal Familial Insomnia
Author(s) -
Dorandeu Anne,
Wingertsmann Laure,
Chrétien Fabrice,
Delisle MarieBernadette,
Vital Claude,
Parchi Piero,
Montagna Pasquale,
Lugaresi Elio,
Ironside James W.,
Budka Herbert,
Gambetti Pierluigi,
Gray Françoise
Publication year - 1998
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.1998.tb00175.x
Subject(s) - neocortex , thalamus , biology , cerebellum , cerebral cortex , immunostaining , fatal familial insomnia , basal ganglia , neuroscience , methionine , pathology , central nervous system , genetics , disease , medicine , immunohistochemistry , immunology , amino acid , prion protein
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 feature, we examined samples of thalamus, basal ganglia, cerebral cortex, cerebellum and medulla from 10 subjects with FFI. All the patients had the characteristic 178 N mutation of the PrP gene. Eight subjects were homozygous methionine/methionine at codon 129 and 2 were heterozygous methionine/valine. Apoptotic neurons were identified by in situ 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 seemed 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 activation as demonstrated by the expression of major histocompatibility complex class II antigens. PrP res immunostaining was almost invariably negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrP res deposits in prion diseases.