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. 2021 Jul 29;142(4):707–728. doi: 10.1007/s00401-021-02350-y

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Mutation-specific histopathological variations across the spectrum of gCJD phenotypes. a Modified, “thickened” synaptic pattern of PrP deposition in the molecular layer of cerebellum in a patient carrying the E200K-129M haplotype. b, c Granular PrP deposits with long-thin (b) and short-thick (c) stripe-like appearance distributed perpendicularly to the surface in the molecular layer of cerebellum in 6- and 4-OPRI-129M carriers, respectively. d Round patches of fine, granular PrP deposits in the deep frontal cortex of a 4-OPRI-129M case. e Multiple, small PrP-amyloid plaques in the cerebellar molecular layer in a E211Q-129M carrier. f, g Multiple, intraneuronal globular PrP deposits distributed in the perikaryon in a E200K-129V individual with PrP^Sc type 2 (f, deep layers of frontal cortex) and E200K-129M with PrP^Sc type “i” (g, pons). h–k Spongiform change characterized by small and intermediate, non-confluent vacuoles in the caudate nucleus, and granular/mini plaque-like PrP deposits in the striatum and molecular layer of cerebellum of patients with T183A-129M (h, i) and atypical 6-OPRI-129V (j, k), respectively. Immunohistochemistry for PrP with mAb 3F4 (a–g, i, k), and haematoxylin–eosin staining (h, j)