NR AFFN
AU Hauw,J.J.; Sazdovitch,V.; Laplanche,J.L.; Peoc'h,K.; Kopp,N.; Kemeny,J.; Privat,N.; Delasnerie-Laupretre,N.; Brandel,J.P.; Deslys,J.P.; Dormont,D.; Alperovitch,A.
TI Neuropathologic variants of sporadic Creutzfeldt-Jakob disease and codon 129 of PrP gene
QU Neurology 2000 Apr 25; 54(8): 1641-6
PT journal article
AB OBJECTIVES: To determine the contribution of methionine/valine (Met/Val) polymorphism at codon 129 of the prion protein (PrP) gene in the neuropathologic pattern and mechanisms of lesion development in sporadic Creutzfeldt-Jakob disease. BACKGROUND: Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized by a conformational change of PrP and a variety of PrP deposits in the brain, some of which aggregate into amyloid plaques. METHODS: The authors semiquantitatively assessed neuropathologic lesions and performed PrP immunolabeling in 70 patients (39 Met/Met, 11 Met/Val, 20 Val/Val) who had died in France between 1994 and 1998. RESULTS: Met/Met cases (mild lesions mostly involving the occipital areas, low PrP load, few focal PrP nonamyloid deposits, no amyloid plaques) contrasted with Met/Val cases (marked lesions especially in the parahippocampal gyrus, high PrP load, numerous amyloid plaques) and with Val/Val cases (younger patients, longer course of disease: 11.5 +/- 3 months, and distinct neuropathology: severe lesions heavily involving the hippocampal formation and basal ganglia, high PrP load, numerous focal nonamyloid deposits, rare amyloid plaques). The course of Val/Val patients younger than age 55 was particularly long (19.9 +/- 7 months), and the isocortex bore the brunt of the pathology, suggesting a distinct variety. CONCLUSIONS: Polymorphism at codon 129 modulates the phenotype of sporadic Creutzfeldt-Jakob disease. The Val genotype enhances the production of proteinase-resistant PrP, and the Met/Val genotype facilitates its aggregation into amyloid plaques.
MH Age Distribution; Aged; Amino Acid Substitution/genetics; Brain/metabolism/pathology; Codon/*genetics; Creutzfeldt-Jakob Syndrome/*epidemiology/*genetics/pathology; DNA Mutational Analysis; Disease Progression; France/epidemiology; Genotype; Human; Immunohistochemistry; Middle Age; Mutation, Missense; Phenotype; Polymorphism (Genetics)/genetics; Prions/*genetics/metabolism; Support, Non-U.S. Gov't
AD Raymond Escourolle Neuropathology Laboratory, Pitie-Salpetriere Hospital, Paris, France. jean-jazques.hauw@psl.ap-hop-paris.fr
SP englisch
PO USA