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Prion protein heterogeneity in sporadic but not variant Creutzfeldt–Jakob disease: U.K. cases 1991–2002
Author(s) -
Head Mark W.,
Bunn Tristan J. R.,
Bishop Matthew T.,
McLoughlin Victoria,
Lowrie Suzanne,
McKimmie Clive S.,
Williams Michelle C.,
McCardle Linda,
MacKenzie Jan,
Knight Richard,
Will Robert G.,
Ironside James W.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20127
Subject(s) - disease , neurodegeneration , creutzfeldt jakob syndrome , prion protein , virology , infectious agent , kuru , biology , autopsy , degenerative disease , pathology , medicine , scrapie
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. Ann Neurol 2004;55:851–859