Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: UK cases 1991-2002.
Human prion diseases can occur as an idiopathic disorder (sporadic Creutzfeldt-Jakob disease) or can be acquired, as is the case for variant Creutzfeldt-Jakob disease. These disorders are characterized by the accumulation of a protease-resistant form of the host-encoded prion protein termed PrP(Sc) in the brains of affected individuals. PrP(Sc) has been proposed to be the principal, if not sole, component of the infectious agent, with its accumulation in the central nervous system the primary event leading to neurodegeneration. A major question remains as to whether self-propagating structural differences in PrP(Sc) might account for the clinicopathological diversity evident in Creutzfeldt-Jakob disease and whether different prion protein types underlie the existence of different strains of causative agent. Here, we describe the results of a large-scale biochemical study of PrP(Sc) from autopsy-proved cases of variant Creutzfeldt-Jakob disease (n = 59) and compare these with cases of sporadic Creutzfeldt-Jakob disease (n = 170) in the United Kingdom over the period 1991 to 2002. The results show PrP(Sc) in variant Creutzfeldt-Jakob disease to be remarkably stereotyped. In contrast, considerable heterogeneity in PrP(Sc) exists both between and within cases of sporadic Creutzfeldt-Jakob disease.
Head
Mark W
MW
National Creutzfeldt-Jakob Disease Surveillance Unit and Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, United Kingdom. m.w.head@ed.ac.uk
Bunn
Tristan J R
TJ
Bishop
Matthew T
MT
McLoughlin
Victoria
V
Lowrie
Suzanne
S
McKimmie
Clive S
CS
Williams
Michelle C
MC
McCardle
Linda
L
MacKenzie
Jan
J
Knight
Richard
R
Will
Robert G
RG
Ironside
James W
JW
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000635:transmission; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018620:PrPSc Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology
D018620:PrPSc Proteins; D020033:Protein Isoforms