دورية أكاديمية
Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease
| العنوان: | Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease |
|---|---|
| المؤلفون: | Huertas Fernández, Ismael, Jesús, Silvia, García Gómez, Francisco Javier, Lojo, José Antonio, Bernal Bernal, Inmaculada, Bonilla Toribio, Marta, Martín Rodríguez, Juan Francisco, García Solís, David, Gómez Garre, María del Pilar, Mir Rivera, Pablo |
| المساهمون: | Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS), Universidad de Sevilla. Departamento de Medicina, Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (ISCIII-FEDER), Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía. Consejería de Salud y Bienestar Social, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2024 |
| المجموعة: | idUS - Deposito de Investigación Universidad de Sevilla |
| الوصف: | The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study’s objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients. The degree of dopaminergic depletion was investigated with [123I]FP-CIT SPECTs and the presence of dementia was ascertained with a long-term review based on established criteria. The association between genetic and imaging parameters was studied with linear regression, and the relationship with dementia onset with Cox regression. We found that APOE2 allele (Pput = 0.002; Pcau = 0.01), the minor allele 'G' in SNCA polymorphism (Pput = 0.02; Pcau = 0.006) and GBA deleterious variants in (Pput = 0.01; Pcau = 0.001) had a detrimental effect on striatal [123I]FP-CIT uptake in PD. Conversely, Met/Met carriers in COMT polymorphism had increased caudate uptake (Pcau = 0.03). The development of dementia was influenced by APOE4 allele (HR = 1.90; P = 0.03) and GBA deleterious variants (HR = 2.44; P = 0.01). Finally, we observed no role of MAPT locus in any of the syndromes. As a conclusion, APOE2, SNCA, COMT and GBA influence frontostriatal dysfunction whereas APOE4 and GBA influence the development of dementia, suggesting a double-edged role of GBA. The dichotomy of the dual syndromes may be driven by a broad dichotomy in these genetic factors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | PLoS ONE, 12 (4), e0175560.; PI14/01823; PI16/01575; CVI-02526; CTS-7685; PI-0437-2012; PI-0471/2013; https://doi.org/10.1371/journal.pone.0175560Test; https://idus.us.es/handle//11441/154826Test |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0175560Test https://idus.us.es/handle//11441/154826Test |
| حقوق: | Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.29876B46 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |