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

Abstract

In Creutzfeldt-Jakob disease (CJD), the type (type 1 and type 2) of abnormal isoform of prion protein (PrP^Sc) 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 PrP^Sc 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 PrP^Sc 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 PrP^Sc, exept for the different PK-cleavage sites. On the basis of these findings, we hypothesized that (1) type 1 and type 2 PrP^Sc may have distinct aggregation sizes and (2) PrP^Sc from a patient with PrP amyloid plaques in the brain has a larger aggregation size than PrP^Sc from a patient with synaptic non-amyloid type PrP deposits in the brain.