Western Blots Illustrating the Principle of PrP^Sc Profiling and the Co-Occurrence of Multiple PrP^Sc Types within One Patient with sCJD

<div><p>(Upper panel) The PrP^Sc content in various central nervous system regions (indicated below respective lanes) was quantified by plotting the signal intensity on a standard curve created by a serially diluted PrP^Sc standard (standard 1 to 3). Proteinase K digestion is indicated above lanes.</p> <p>(Lower panel) Presence of a faster-migrating unglycosylated band of PrP^Sc (∼19 kDa, PrP^Sc type 2, frontal and temporal cortex) and a slower-migrating unglycosylated band of PrP^Sc (∼21 kDa, PrP^Sc type 1, occipital cortex) within one patient with sCJD (codon 129 MM). Controls include PrP^Sc type 1 and 2 and a sample from a non prion-diseased individual. Proteinase K digestion is indicated above lanes.</p></div

Histological Analysis of Central-Nervous-System Sections in One Patient with sCJD with Co-Occurrence of Multiple PrP^Sc Types

<p>H&E-stained (A and B) and PrP-immunostained (C and D) cortical areas showing pronounced spongiosis and deposition of PrP^Sc in a plaque-like (C; PrP^Sc type 2, see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030014#pmed-0030014-g002" target="_blank">Figure 2</a>, frontal area on the lower panel) and synaptic (D; PrP^Sc type 1, see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030014#pmed-0030014-g002" target="_blank">Figure 2</a>, occipital area on the lower panel) pattern.</p

Comparison of PrP^Sc Profiles to Lesion Profiles

<div><p>(A) Schematic drawing indicating sampled areas which are used for the generation of PrP^Sc profiles (red boxes).</p> <p>(B) Biochemical PrP^Sc profiles are indicated in the upper panel, whereas histological lesion profiles are shown in the lower panel. Patients were grouped according to [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030014#pmed-0030014-b012" target="_blank">12</a>] in MM1, MV1, MV2, and VV2. Brain regions are shown on the <i>x</i>-axis. Values for PrP^Sc amounts are given in arbitrary units measured in relation to the PrP^Sc standard. Values for lesion profiles were obtained by averaging the scores for spongiosis (scored on a scale from 0–4), astrogliosis, and PrP immunoreactivity (both scored on a scale from 0–3). Black dots represent individual patients and black lines within boxes represent medians; boxes encompass 25th and 75th percentiles of distribution. One outlier (denoted by asterisk: MV2, cerebellum, PrP^Sc content = 84.1) has been omitted in the graphical representation.</p></div