FIGURE 2.

Concentration and dichotomous impact of PK treatment on the conformational stability of PrP^Sc isoforms in the cortex of sCJD with mixed type 1 + 2 PrP^Sc in the same location. A, concentration of total and type 1 rPrP^Sc in the cortex of 36 cases of sCJD homozygous for different codon 129 polymorphisms and with WB classification of MM type 1 (n = 10), MM type 2 (n = 10), VV type 2 (n = 10), and MM type 1 + 2 (n = 6) rPrP^Sc in the same location. B, relative proportion of type 1 rPrP^Sc in each codon 129 polymorphism and WB classification group; the sCJD cases MM type 1 + 2 (n = 6) studied in detail in this paper are depicted as brown circles. C, concentrations of total PrP^Sc (purple circles), rPrP^Sc (black circles), sPrP^Sc (green diamonds). D, relative proportion of sPrP^Sc (green diamonds), type 1 (red triangles), and type 2 (blue triangles) in each sCJD case (n = 6). E, distinct conformational stability of total rPrP^Sc, type 1 rPrP^Sc, and incongruent impact of proteinase K treatment (−/+). The same color symbols and links indicate data obtained in the same mixed case of sCJD. F, differential stability curves of type 2 rPrP^Sc obtained after subtracting stability curves of type 1 rPrP^Sc obtained with mAb 12B2 from stability curves of total rPrP^Sc obtained with mAb 3F4 after PK treatment. The CDI with europium-labeled mAb 3F4 was used to determine the concentration and stability of total PrP^Sc and mAb 12B2 to measure the concentration and stability of type 1 rPrP^Sc. Each data point represents a unique patient measured in triplicate, and the concentration of PrP^Sc in 10% brain homogenate was calculated; the percentage of rPrP^Sc or type 1 is expressed over total rPrP^Sc. The horizontal line represents mean for each parameter.