In Creutzfeldt-Jakob disease (CJD), the type (type 1 or 2) of abnormal isoform of the prion protein (PrPSc) in the brain and the genotype at codon 129 of the PrP gene are major determinants of clinicopathological phenotype. Little is known about the difference in biochemical properties between the two types of PrPSc, except for the different proteinase K cleavage sites. To investigate the size of aggregates formed by PrPSc types 1 and 2, brain homogenates from various cases of CJD with the same genotype (homozygous for methionine at codon 129) were passed through filters with a mean pore size of 72±4 nm. Type 2 PrPSc was efficiently removed from the filtrates by the filters, in contrast to type 1. Even type 2 PrPSc from a patient without amyloid plaques was removed more efficiently than type 1 from patients with amyloid plaques. These results indicate that type 2 PrPSc has a larger aggregation size than type 1, irrespective of the existence of amyloid plaques.
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