Type 1 and type 2 human PrPSc have different aggregation sizes in methionine homozygotes with sporadic, iatrogenic and variant Creutzfeldt-Jakob disease

In Creutzfeldt-Jakob disease (CJD), the type (type 1 and type 2) of abnormal isoform of prion protein (PrPSc) in the brain and the genotype at codon 129 of the PrP gene are major determinants of the clinicopathological phenotype. Type 1 and type 2 PrPSc are distinguished by the size of proteinase K (PK) resistant core (21 and 19 kDa), reflecting differences in the PK-cleavage site. Moreover, type 2 PrPSc can be subclassified into type 2A and type 2B by the difference in ratio of glycoforms. However, little is known about the difference in biochemical properties between the two types of PrPSc, exept for the different PK-cleavage sites. On the basis of these findings, we hypothesized that (1) type 1 and type 2 PrPSc may have distinct aggregation sizes and (2) PrPSc from a patient with PrP amyloid plaques in the brain has a larger aggregation size than PrPSc from a patient with synaptic non-amyloid type PrP deposits in the brain.