TY - JOUR
T1 - Huntingtin CAG repeats in neuropathologically confirmed tauopathies :
T2 - Novel insights
AU - Pérez-Oliveira, Sergio
AU - Castilla-Silgado, Juan
AU - Painous, Cèlia
AU - Aldecoa, Iban
AU - Mendez-Gonzalez, Manuel
AU - Blázquez Estrada, Marta
AU - Corte, Daniela
AU - Tomás-Zapico, Cristina
AU - Compta, Yaroslau
AU - Muñoz García, José Esteban
AU - Llado Plarrumani, Albert
AU - Balasa, Mircea
AU - Aragonès, Gemma
AU - García-González, Pablo
AU - Rosende-Roca, Maitée
AU - Boada, Mercè
AU - Ruíz, Agustín
AU - Pastor, Pau
AU - De la Casa-Fages, Beatriz
AU - Rábano, Alberto
AU - Sanchez-Valle, Raquel
AU - Molina-Porcel, L.
AU - Alvarez, Victoria
PY - 2024/2/28
Y1 - 2024/2/28
N2 - 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.
AB - 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.
KW - Alzheimer disease
KW - corticobasal degeneration
KW - HTT gene
KW - progressive supranuclear palsy
KW - tauopathies
UR - http://www.scopus.com/inward/record.url?scp=85186629546&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/5681260a-8445-3866-91ce-ea00a8cf121d/
U2 - 10.1111/bpa.13250
DO - 10.1111/bpa.13250
M3 - Article
C2 - 38418081
SN - 1015-6305
VL - 34
JO - Brain Pathology
JF - Brain Pathology
IS - 4
M1 - e13250
ER -