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Apolipoproteína E4 y sus efectos en la salud en la población con esclerosis múltiple
Dean Zeldich1, Chia Hsin Cheng2, Yi Guan2
1Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
Resumen
El alelo de apolipoproteína E4 (APOE4) empeora la neuroinflamación y la neurodegeneración en pacientes con esclerosis múltiple (EM). Este factor genético exacerba la progresión de la EM, afectando la función cognitiva y la salud cerebral, como lo demuestran biomarcadores multidominio.
Área de la Ciencia:
- Neuroinmunología
- Genética
- Neurología
Sus antecedentes:
- La esclerosis múltiple (EM) es una enfermedad autoinmune crónica caracterizada por neuroinflamación y neurodegeneración.
- El alelo de apolipoproteína E4 (APOE4) es un factor de riesgo genético significativo para la enfermedad de Alzheimer, conocido por acelerar el deterioro cognitivo y los procesos neuroinflamatorios.
Objetivo del estudio:
- Investigar el impacto del alelo APOE4 en los resultados de salud de los pacientes con esclerosis múltiple.
- Explorar el papel del APOE4 en la exacerbación de la neurodegeneración y la neuroinflamación en el contexto de la EM.
Principales métodos:
- Se utilizaron datos del UK Biobank, agrupando a los pacientes con EM según el estado de portador de APOE4 (EM-E4 vs. EM no portador de E4).
- Se incluyeron controles sin EM emparejados por edad y sexo (control-E4 vs. control no portador de E4).
- Se evaluó el grosor de la capa de fibras nerviosas de la retina (RNFL) mediante OCT, biomarcadores sanguíneos (GFAP, NfL), rendimiento cognitivo y métricas de resonancia magnética cerebral.
Principales resultados:
- Los pacientes con EM y el alelo APOE4 (EM-E4) mostraron peores resultados: RNFL más delgado, GFAP y NfL elevados, tiempos de reacción cognitiva más lentos y aumento de las hiperintensidades de la materia blanca.
- Los niveles de proteína ácida fibrilar glial (GFAP) demostraron interacciones significativas entre el estado de EM y APOE4, correlacionándose con marcadores de neurodegeneración.
- Se observaron efectos perjudiciales similares del APOE4 en individuos de control sanos.
Conclusiones:
- APOE4 exacerba significativamente la neurodegeneración y la neuroinflamación en pacientes con EM.
- Los biomarcadores multidominio, incluida la OCT retiniana, las pruebas cognitivas y la RM, son valiosos para monitorizar la progresión de la EM.
- Los biomarcadores menos invasivos muestran ser prometedores para seguir el avance de la enfermedad en la EM.
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