Immunoblot analysis of purified detergent insoluble fractions (P3) of PrP from the cerebral cortex of one control subject (lane 6) and two subjects (2 and 7) with GSS P102L (lanes 2–5), before (lanes 1, 2, 4, and 6) and after PK digestion (lanes 3 and 5). Although in the control (lane 6), no PrP is detectable in the insoluble fraction not treated with PK, in both GSS samples, significant amount of truncated PrP fragments, in addition to some full-length PrP, are present. However, pattern and properties of the truncated PrP peptides are different in the two GSS cases. In subject 2 (lane 2), there are large amount of 29-, 27-, and 21-kDa fragments that comigrate with the PrP-res peptides visible after PK treatment. In addition, two bands migrating at 11- and 9-kDa are present. Patient 7 (lane 4) shows similar bands at 29, 27, and 21 kDa, but only before PK treatment, indicating that these peptides are insoluble but not protease resistant. In addition, a band at 8 kDa that has similar intensity and comigrates with the PrP-res fragment is visible. Full-length PrP from a crude homogenate of the control subject is represented in lane 1.