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Alfie Wearn1, Christine L Tardif2,3, Ilana R Leppert3,4

  • 1Montreal Neurological Institute, McGill University, Montreal, QC, Canada.

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|December 23, 2025
PubMed
Resumen
Este resumen es generado por máquina.

La integridad del locus coeruleus (LC) está relacionada con la patología de amiloide y tau en individuos asintomáticos con enfermedad de Alzheimer (EA). Esto sugiere que el LC juega un papel clave en la patogénesis temprana de la EA, incluso antes de que aparezcan los síntomas.

Palabras clave:
locus coeruleusenfermedad de Alzheimeramiloidetauneuroimagenestudios longitudinalesasintomático

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Área de la Ciencia:

  • Neurociencia
  • Neuropatología
  • Radiología

Sus antecedentes:

  • El locus coeruleus (LC) es un sitio temprano de patología tau en la enfermedad de Alzheimer (EA), que precede a los síntomas clínicos.
  • Investigar la integridad del LC en relación con la deposición de amiloide y tau es crucial para comprender la EA preclínica.

Objetivo del estudio:

  • Determinar si la integridad del locus coeruleus (LC) se asocia con la deposición cortical de amiloide y tau in vivo en adultos mayores asintomáticos y en riesgo.
  • Explorar la relación entre la integridad del LC y los primeros signos de la EA.

Principales métodos:

  • Se utilizó MRI de 3T e imágenes PET (18F-NAV4694 para amiloide, 18F-flortaucipir para tau) en 208 adultos mayores sanos con antecedentes familiares de EA.
  • Se cuantificó la integridad del LC utilizando imágenes del tronco encefálico sensibles a la neuromelanina (LCCNR) y la deposición cortical regional de amiloide/tau (SUVR).
  • Se emplearon modelos robustos de efectos mixtos lineales y regresión lineal, corrigiendo por edad, sexo y educación, con ajuste FDR para los valores p.

Principales resultados:

  • Se encontraron asociaciones negativas entre la integridad del LC y el SUVR de amiloide cortical en la mayoría de las regiones.
  • La integridad del LC mostró asociaciones con la tau cortical en las regiones temporal e inferoparietal, particularmente en el hemisferio izquierdo.
  • Estas asociaciones estuvieron presentes al inicio, no longitudinalmente, y la relación tau-LC fue modulada por los niveles globales de amiloide.

Conclusiones:

  • La degeneración del locus coeruleus (LC) se correlaciona con un aumento de la patología de amiloide y tau en individuos asintomáticos con factores de riesgo de EA.
  • Estos hallazgos respaldan el modelo del LC como un actor central en los cambios fisiopatológicos más tempranos de la enfermedad de Alzheimer.