Neuronal Apoptosis in Fatal Familial Insomnia

Brain Pathology - Tập 8 Số 3 - Trang 531-537 - 1998
Anne Dorandeu1, José Carlos Fernández Fernández2, Claire Leconte2, Marie‐Bernadette Delisle3, C Vital4, Piero Parchi5, Pasquale Montagna6, E Lugaresi6, James Ironside7, Herbert Budka8, Pierluigi Gambetti5, Françoise Gray2,1
1Laboratoire de Neuropathologie, Faculté de Médecine Paris-Ouest, Garches, France.
2Laboratoire d'Histologie, Embryologie et Cytogénétique, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
3Laboratoire d'Anatomie Pathologique, Faculté de Médecine Rangueil, Toulouse, France.
4Laboratoire de Neuropathologie, Université Victor Ségalen, Bordeaux, France.
5Division of Neuropathology, Institute of Pathology, Case Western University, Cleveland, Ohio, USA.
6Institute of Clinical Neurology, University of Bologna, Bologna, Italy
7Neuropathology Laboratory, Department of Pathology, the University of Edinburgh, Edinburgh, UK.
8Institute of Neurology, University of Vienna, Vienna, Austria

Tóm tắt

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. PrPres immunostaining was almost invariably negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrPres deposits in prion diseases.

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Brain Pathology

Tập 8 Số 3

531-537

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