RT Journal Article
T1 Systematic Screening of Ubiquitin/p62 Aggregates in Cerebellar Cortex Expands the Neuropathological Phenotype of the C9orf72 Expansion Mutation.
A1 Ramos-Campoy, Oscar
A1 Ávila-Polo, Rainiero
A1 Grau-Rivera, Oriol
A1 Antonell, Anna
A1 Clarimón, Jordi
A1 Rojas-García, Ricardo
A1 Charif, Sara
A1 Santiago-Valera, Veronica
A1 Hernandez, Isabel
A1 Aguilar, Miquel
A1 Almenar, Consuelo
A1 Lopez-Villegas, Dolores
A1 Bajo, Lorena
A1 Pastor, Pau
A1 Van der Zee, Julie
A1 Lladó, Albert
A1 Sanchez-Valle, Raquel
A1 Gelpi, Ellen
AB 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.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12573
UL http://hdl.handle.net/10668/12573
LA en
DS RISalud
RD Apr 8, 2025