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Ciencia básica y patogénesis

Clémentine Puech1, Anjana Sadanand2, Neil Coleman2

  • 1University of Missouri, Columbia, MO, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

La enfermedad de Alzheimer (EA) afecta más a las mujeres, lo que podría estar relacionado con problemas de sueño. La señalización de APP mejoró el sueño y la memoria en un modelo de ratón, con efectos más fuertes en las hembras, lo que pone de relieve las diferencias cerebrales específicas del sexo en la salud.

Palabras clave:
Enfermedad de AlzheimerProteína precursora amiloideDominio intracelular de la proteína precursora amiloideSeñalización GαsBarrera hematoencefálicaSueñoFunción cognitivaModelos de ratónDiferencias sexualesNeurociencia

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Área de la Ciencia:

  • Neurociencia
  • Genética
  • Biología Molecular

Sus antecedentes:

  • La enfermedad de Alzheimer (EA) afecta desproporcionadamente a las mujeres mayores de 65 años.
  • Las alteraciones del sueño son un indicador temprano y un factor de riesgo de la EA, y perjudican la eliminación del amiloide-beta (Aβ).
  • El papel de la señalización intracelular de la proteína precursora de amiloide (APP) en el sueño y la EA sigue sin estar claro.

Objetivo del estudio:

  • Investigar si el dominio intracelular de APP (mAICD) y su señalización Gαs afectan la integridad del sueño y la barrera hematoencefálica (BHE) en el modelo de ratón AD 5XFAD.
  • Determinar los efectos específicos del sexo de la señalización de mAICD en la función cognitiva y la integridad de la BHE.

Principales métodos:

  • Administración de virus adenoasociados (AAV) de mAICD y una variante que no interactúa con Gαs en ratones 5XFAD neonatales.
  • Evaluación de los patrones de sueño, los comportamientos cognitivos y la integridad de la BHE en ratones machos y hembras adultos.

Principales resultados:

  • La señalización mediada por APP mitigó la disminución de la memoria relacionada con las alteraciones del sueño en ratones 5XFAD.
  • Emergieron diferencias sexuales en el rendimiento cognitivo en ratones 5XFAD, con un mejor rendimiento correlacionado con el sueño en las hembras.
  • Las medidas del sueño y la integridad de la BHE se correlacionaron, particularmente en ratones hembra, lo que indica un deterioro neurovascular dependiente del sexo.

Conclusiones:

  • La señalización de APP juega un papel importante en la restauración del sueño y la memoria en un modelo de ratón AD.
  • Existe una fuerte relación entre el rendimiento cognitivo y la fuga de la BHE en ratones hembra, lo que sugiere una disfunción neurovascular dependiente del sexo.
  • Los hallazgos subrayan la importancia de la señalización de APP en la patogénesis de la EA y los posibles objetivos terapéuticos específicos del sexo.