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Huntingtin CAG repeats in neuropathologically confirmed tauopathies: Novel insights.

Authors :
Pérez‐Oliveira, Sergio
Castilla‐Silgado, Juan
Painous, Cèlia
Aldecoa, Iban
Menéndez‐González, Manuel
Blázquez‐Estrada, Marta
Corte, Daniela
Tomás‐Zapico, Cristina
Compta, Yaroslau
Muñoz, Esteban
Lladó, Albert
Balasa, Mircea
Aragonès, Gemma
García‐González, Pablo
Rosende‐Roca, Maitée
Boada, Mercè
Ruíz, Agustín
Pastor, Pau
De la Casa‐Fages, Beatriz
Rabano, Alberto
Source :
Brain Pathology; Jul2024, Vol. 34 Issue 4, p1-15, 15p
Publication Year :
2024

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10156305
Volume :
34
Issue :
4
Database :
Complementary Index
Journal :
Brain Pathology
Publication Type :
Academic Journal
Accession number :
178021087
Full Text :
https://doi.org/10.1111/bpa.13250