| Title: |
Huntingtin CAG repeats in neuropathologically confirmed tauopathies : Novel insights |
| Authors: |
Pérez-Oliveira, Sergio; Castilla-Silgado, Juan; Painous, Cèlia; Aldecoa, Iban; Mendez-Gonzalez, Manuel; Blázquez Estrada, Marta; Corte, Daniela; Tomás-Zapico, Cristina; Compta, Yaroslau; Muñoz García, José Esteban; Llado Plarrumani, Albert; Balasa, Mircea; Aragonès, Gemma; García-González, Pablo; Rosende-Roca, Maitée; Boada, Mercè; Ruiz Laza, Agustín; Pastor, Pau; De la Casa-Fages, Beatriz; Rábano, Alberto; Sanchez-Valle, Raquel; Molina-Porcel, L.; Alvarez, Victoria |
| Publication Year: |
2024 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
Alzheimer disease; Corticobasal degeneration; HTT gene; Progressive supranuclear palsy; Tauopathies |
| Description: |
Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
17503639 |
| Relation: |
Ministerio de Economía y Competitividad PI13/02434; Ministerio de Economía y Competitividad PI16/01861; Instituto de Salud Carlos III PI17/01474; Instituto de Salud Carlos III PI19/01301; Instituto de Salud Carlos III PI22/01403; Instituto de Salud Carlos III PMP22/00022; Brain pathology; Vol. 34 Núm. 4 (july 2024), p. e13250; https://ddd.uab.cat/record/301970; urn:10.1111/bpa.13250; urn:oai:ddd.uab.cat:301970; urn:scopus_id:85186629546; urn:articleid:17503639v34n4e13250; urn:pmid:38418081; urn:pmcid:PMC11189778; urn:oai:pubmedcentral.nih.gov:11189778 |
| Availability: |
https://ddd.uab.cat/record/301970 |
| Rights: |
open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.F3C4C071 |
| Database: |
BASE |