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MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features.
Valentino, Rebecca R; Koga, Shunsuke; Walton, Ronald L; Soto-Beasley, Alexandra I; Kouri, Naomi; DeTure, Michael A; Murray, Melissa E; Johnson, Patrick W; Petersen, Ronald C; Boeve, Bradley F; Uitti, Ryan J; Wszolek, Zbigniew K; Dickson, Dennis W; Ross, Owen A; Heckman, Michael G.
Afiliación
  • Valentino RR; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Koga S; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Walton RL; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Soto-Beasley AI; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Kouri N; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • DeTure MA; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Murray ME; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Johnson PW; Division of Biomedical Statistics and Informatics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Petersen RC; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • Boeve BF; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • Uitti RJ; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Wszolek ZK; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Dickson DW; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. dickson.dennis@mayo.edu.
  • Ross OA; Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
  • Heckman MG; Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA.
Acta Neuropathol Commun ; 8(1): 218, 2020 12 07.
Article en En | MEDLINE | ID: mdl-33287913
The microtubule-associated protein tau (MAPT) H1 haplotype is the strongest genetic risk factor for corticobasal degeneration (CBD). However, the specific H1 subhaplotype association is not well defined, and it is not clear whether any MAPT haplotypes influence severity of tau pathology or clinical presentation in CBD. Therefore, in the current study we examined 230 neuropathologically confirmed CBD cases and 1312 controls in order to assess associations of MAPT haplotypes with risk of CBD, severity of tau pathology (measured as semi-quantitative scores for coiled bodies, neurofibrillary tangles, astrocytic plaques, and neuropil threads), age of CBD onset, and disease duration. After correcting for multiple testing (P < 0.0026 considered as significant), we confirmed the strong association between the MAPT H2 haplotype and decreased risk of CBD (Odds ratio = 0.26, P = 2 × 10-12), and also observed a novel association between the H1d subhaplotype and an increased CBD risk (Odds ratio = 1.76, P = 0.002). Additionally, although not statistically significant after correcting for multiple testing, the H1c haplotype was associated with a higher risk of CBD (Odds ratio = 1.49, P = 0.009). No MAPT haplotypes were significantly associated with any tau pathology measures, age of CBD onset, or disease duration. Though replication will be important and there is potential that population stratification could have influenced our findings, these results suggest that several MAPT H1 subhaplotypes are primarily responsible for the strong association between MAPT H1 and risk of CBD, but that H1 subhaplotypes are unlikely to play a major role in driving tau pathology or clinical features. Our findings also indicate that similarities in MAPT haplotype risk-factor profile exist between CBD and the related tauopathy progressive supranuclear palsy, with H2, H1d, and H1c displaying associations with both diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Proteínas tau / Tauopatías Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Acta Neuropathol Commun Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Proteínas tau / Tauopatías Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Acta Neuropathol Commun Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido