Figure 1

Threads of PrP positive deposits in inherited prion diseases with 4 and 6 octapeptide repeat insert mutation, P102L (Gerstmann Sträussler-Scheinker syndrome), and A117V mutation. AD, 4OPRI mutation with abundant threads, which form a dense crisscrossing network (corresponding to myelinated fibres) in the cortex (A) and forming multiple, thin parallel threads in the subcortical white matter, detectable with two antibodies, ICSM35 (B) and KG9 (C). Arrowheads in B and C point to accentuated threads. In the cerebellum (D), the PrP-containing filaments are thicker, shorter, and less abundant than in the cortex. The 6OPRI mutation (E-H) is characterised by abundant threads in the cortical grey matter I, subcortical white matter (F, ICSM35, G, KG9), and in the cerebellar granular layer (H). I-L, Both forebrain and cerebellum with PRNP P102L mutations show white matter threads of abnormal PrP in the subcortical (J, ICSM35 and K, KG9) or cerebellar (L) white matter. Arrows I-L show short threads of PrP deposition. Small myelinated fibres extending into the cerebral cortex also show threads of abnormal PrP (arrowhead in I) alongside with large amyloid plaques (not shown) and synaptic PrP. M-Q, A117V mutation (Case #16 M-P and Case #17, Q) with abundant cortical threads (M), corresponding to myelinated cortical fibres. The inset shows several parallel threads. Also the subcortical white matter is rich in PrP positive threads (N, ICSM35 and O, KG9). The cerebellum of the same case lacks filamentous inclusions, whilst small granular deposits are often observed (P). The brain stem of case #17 shows cross sections of myelinated fibres with occasional circular PrP-positive structures, corresponding to PrP containing myelin sheaths. Scale bar corresponds to 20 μm in P, 40 μm in the insets of E, F, H and M, to 80 μm in C, G, H, O and to 140 μm in all other panels.