NR AJFA
AU Parchi,P.; Castellani,R.J.; Cortelli,P.; Montagna,P.; Chen,S.G.; Petersen,R.B.; Manetto,V.; Vnencak-Jones,C.L.; McLean,M.J.; Sheller,J.R.; Lugaresi,E.; Autilio-Gambetti,L.; Gambetti,P.
TI Regional distribution of protease-resistant prion protein in fatal familial insomnia
QU Annals of Neurology 1995 Jul; 38(1): 21-9
PT journal article
AB Protease-resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia. Six were homozygotes methionine/methionine at codon 129 (mean duration, 10.7 +/- 4 months) and 3 were heterozygotes methionine/valine (mean duration, 23 +/- 11 months). In all subjects, protease-resistant prion protein was detected in gray matter but not in white matter and peripheral organs. Its distribution was more widespread than that of the histopathological lesions, which were observed only in the presence of a critical amount of the abnormal protein. In the mediodorsal thalamic nucleus, however, a severe neuronal loss and astrogliosis were associated with relatively moderate amounts of protease-resistant prion protein, suggesting a higher vulnerability. There was no overall correlation between amount of protease-resistant prion protein and either glial fibrillary acidic protein or total prion protein. While protease-resistant prion protein was virtually limited to subcortical areas and showed a selective pattern of distribution in the subjects with disease of the shortest duration, it was more widespread in the subjects with a longer clinical course, indicating that with time the disease process spreads within the brain. The kinetics of the accumulation of protease-resistant prion protein varied among different brain regions: While in the neocortex and to a lesser extent in the limbic lobe and in the caudate nucleus, the amount increased with disease duration, in the mediodorsal thalamic nucleus and in the brainstem it was present in comparable amounts in all subjects regardless of the disease duration.(ABSTRACT TRUNCATED AT 250 WORDS)
IN
Von 9 untersuchten Patienten mit der fatalen erblichen Schlaflosigkeit waren 6 homozygot bezüglich Methionin-129, während nur 3 heterozygot mit Valin und Methionin im Codon 129 waren. Bei den Heterozygoten dauerte die Krankheitsphase mit 23+/-11 Monaten durchschnittlich mehr als doppelt so lange wie bei den Homozygoten mit 10,7+/-4 Monaten.
Proteaseresistentes Prionprotein wurde nur in der zellulären grauen Gehirnsubstanz gefunden. Seine Verbreitung war größer als die der histopathologisch erkennbaren Schädigungen, die erst ab bestimmten Konzentrationen des proteaseresistenten Prionproteins auftraten. Dieser Schwellenwert war allerdings in verschiedenen Gehirnregionen unterschiedlich. Bei Patienten mit langsamem Krankheitsverlauf waren die proteaseresistenten Prionproteine weiter und weniger selektiv verbreitet. Die spezifischen Krankheitszeichen entstehen offenbar dadurch, dass die proteaseresistenten Prionproteine in verschiedenen Gehirnregionen unterschiedlich schnell akkumulieren und zusätzlich unterschiedlich toxisch wirken.
ZR 31
MH Adult; *Brain Chemistry; Endopeptidases/metabolism; Glial Fibrillary Acidic Protein/analysis; Human; Immunoblotting; Middle Age; PrPc Proteins/analysis; Prion Diseases/*pathology; Prions/*analysis; *Sleep Initiation and Maintenance Disorders/genetics/pathology; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106-4901, USA
SP englisch
PO USA