Cargando…

Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data

Gerstmann–Sträussler–Scheinker syndrome (GSS) is a hereditary neurodegenerative disease characterized by extracellular aggregations of pathological prion protein (PrP) forming characteristic plaques. Our study aimed to evaluate the micromorphology and protein composition of these plaques in relation...

Descripción completa

Detalles Bibliográficos
Autores principales: Jankovska, Nikol, Matej, Radoslav, Olejar, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704598/
https://www.ncbi.nlm.nih.gov/pubmed/34948096
http://dx.doi.org/10.3390/ijms222413303
_version_ 1784621745121001472
author Jankovska, Nikol
Matej, Radoslav
Olejar, Tomas
author_facet Jankovska, Nikol
Matej, Radoslav
Olejar, Tomas
author_sort Jankovska, Nikol
collection PubMed
description Gerstmann–Sträussler–Scheinker syndrome (GSS) is a hereditary neurodegenerative disease characterized by extracellular aggregations of pathological prion protein (PrP) forming characteristic plaques. Our study aimed to evaluate the micromorphology and protein composition of these plaques in relation to age, disease duration, and co-expression of other pathogenic proteins related to other neurodegenerations. Hippocampal regions of nine clinically, neuropathologically, and genetically confirmed GSS subjects were investigated using immunohistochemistry and multichannel confocal fluorescent microscopy. Most pathognomic prion protein plaques were small (2–10 µm), condensed, globous, and did not contain any of the other investigated proteinaceous components, particularly dystrophic neurites. Equally rare (in two cases out of nine) were plaques over 50 µm having predominantly fibrillar structure and exhibit the presence of dystrophic neuritic structures; in one case, the plaques also included bulbous dystrophic neurites. Co-expression with hyperphosphorylated protein tau protein or amyloid beta-peptide (Aβ) in GSS PrP plaques is generally a rare observation, even in cases with comorbid neuropathology. The dominant picture of the GSS brain is small, condensed plaques, often multicentric, while presence of dystrophic neuritic changes accumulating hyperphosphorylated protein tau or Aβ in the PrP plaques are rare and, thus, their presence probably constitutes a trivial observation without any relationship to GSS development and progression.
format Online
Article
Text
id pubmed-8704598
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87045982021-12-25 Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data Jankovska, Nikol Matej, Radoslav Olejar, Tomas Int J Mol Sci Article Gerstmann–Sträussler–Scheinker syndrome (GSS) is a hereditary neurodegenerative disease characterized by extracellular aggregations of pathological prion protein (PrP) forming characteristic plaques. Our study aimed to evaluate the micromorphology and protein composition of these plaques in relation to age, disease duration, and co-expression of other pathogenic proteins related to other neurodegenerations. Hippocampal regions of nine clinically, neuropathologically, and genetically confirmed GSS subjects were investigated using immunohistochemistry and multichannel confocal fluorescent microscopy. Most pathognomic prion protein plaques were small (2–10 µm), condensed, globous, and did not contain any of the other investigated proteinaceous components, particularly dystrophic neurites. Equally rare (in two cases out of nine) were plaques over 50 µm having predominantly fibrillar structure and exhibit the presence of dystrophic neuritic structures; in one case, the plaques also included bulbous dystrophic neurites. Co-expression with hyperphosphorylated protein tau protein or amyloid beta-peptide (Aβ) in GSS PrP plaques is generally a rare observation, even in cases with comorbid neuropathology. The dominant picture of the GSS brain is small, condensed plaques, often multicentric, while presence of dystrophic neuritic changes accumulating hyperphosphorylated protein tau or Aβ in the PrP plaques are rare and, thus, their presence probably constitutes a trivial observation without any relationship to GSS development and progression. MDPI 2021-12-10 /pmc/articles/PMC8704598/ /pubmed/34948096 http://dx.doi.org/10.3390/ijms222413303 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jankovska, Nikol
Matej, Radoslav
Olejar, Tomas
Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title_full Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title_fullStr Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title_full_unstemmed Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title_short Extracellular Prion Protein Aggregates in Nine Gerstmann–Sträussler–Scheinker Syndrome Subjects with Mutation P102L: A Micromorphological Study and Comparison with Literature Data
title_sort extracellular prion protein aggregates in nine gerstmann–sträussler–scheinker syndrome subjects with mutation p102l: a micromorphological study and comparison with literature data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704598/
https://www.ncbi.nlm.nih.gov/pubmed/34948096
http://dx.doi.org/10.3390/ijms222413303
work_keys_str_mv AT jankovskanikol extracellularprionproteinaggregatesinninegerstmannstrausslerscheinkersyndromesubjectswithmutationp102lamicromorphologicalstudyandcomparisonwithliteraturedata
AT matejradoslav extracellularprionproteinaggregatesinninegerstmannstrausslerscheinkersyndromesubjectswithmutationp102lamicromorphologicalstudyandcomparisonwithliteraturedata
AT olejartomas extracellularprionproteinaggregatesinninegerstmannstrausslerscheinkersyndromesubjectswithmutationp102lamicromorphologicalstudyandcomparisonwithliteraturedata