Systematic screening of ubiquitin/p62 aggregates in cerebellar cortex expands the neuropathological phenotype of the C9orf72 expansion mutation

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• dc.contributor.author Ramos-Campoy, O.
• dc.contributor.author Lopez-Villegas, María Dolores
• dc.contributor.author Gelpi, Ellen
• dc.date.accessioned 2019-06-05T08:23:12Z
• dc.date.issued 2018
• dc.description.abstract The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI). Positive cases were also stained for dipeptide repeats. We identified a total of 21 donors with UPPI and in all of them the C9orf72 hexanucleotide expansion was genetically confirmed. Most donors had an FTLD or to a lesser extent ALS clinico-pathological phenotype. However, 3 cases had been previously classified as having clinically and neuropathologically Lewy body disease. Other co-existing pathologies, especially of the PART-type, were also frequently encountered. This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ramos-Campoy O, Ávila-Polo R, Grau-Rivera O, Antonell A, Clarimón J, Rojas-García R. et al. Systematic screening of ubiquitin/p62 aggregates in cerebellar cortex expands the neuropathological phenotype of the C9orf72 expansion mutation. J Neuropathol Exp Neurol. 2018 Aug 1;77(8):703-709. DOI: 10.1093/jnen/nly047
• dc.identifier.doi http://dx.doi.org/10.1093/jnen/nly047
• dc.identifier.issn 1554-6578
• dc.identifier.uri http://hdl.handle.net/10230/41701
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in journal of neurophatology and experimental neurology following peer review. The version of record Ramos-Campoy O, Ávila-Polo R, Grau-Rivera O, Antonell A, Clarimón J, Rojas-García R. et al. Systematic screening of ubiquitin/p62 aggregates in cerebellar cortex expands the neuropathological phenotype of the C9orf72 expansion mutation. J Neuropathol Exp Neurol. 2018 Aug 1;77(8):703-709 is available online at: https://academic.oup.com/jnen/article-abstract/77/8/703/5034502?redirectedFrom=fulltext. DOI 10.1093/jnen/nly047
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Esclerosi lateral amiotròfica
• dc.subject.other Fenotip
• dc.title Systematic screening of ubiquitin/p62 aggregates in cerebellar cortex expands the neuropathological phenotype of the C9orf72 expansion mutation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion