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Ciencia básica y patogénesis

Pamela Del Rosario1, Alyssa N De Vito2, Colin Stein3

  • 1Columbia University Irving Medical Center, New York, NY, USA.

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

Los síntomas neuropsiquiátricos en la enfermedad de Alzheimer (EA) son comunes e impactan la calidad de vida. Este estudio analiza datos genéticos de diversas poblaciones para identificar causas y desarrollar mejores tratamientos para estos síntomas debilitantes.

Palabras clave:
enfermedad de Alzheimersíntomas neuropsiquiátricosgenéticasecuenciación del genoma completoestudios de cohortestrastornos psicóticos

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Área de la Ciencia:

  • Neurogenética
  • Investigación de la enfermedad de Alzheimer
  • Sintomatología psiquiátrica

Sus antecedentes:

  • Los síntomas neuropsiquiátricos (NPS) son muy prevalentes en pacientes con enfermedad de Alzheimer (EA).
  • Los NPS se asocian con un declive cognitivo acelerado y una menor calidad de vida para pacientes y cuidadores.
  • Las intervenciones farmacéuticas actuales para los NPS en la EA son ineficaces, lo que requiere investigación sobre los mecanismos subyacentes.

Objetivo del estudio:

  • Identificar loci genéticos y vías mecanicistas que contribuyen a los NPS en la EA.
  • Facilitar el desarrollo de estrategias terapéuticas mejoradas para los NPS en la EA.
  • Analizar datos de poblaciones ancestrales diversas para garantizar una amplia aplicabilidad.

Principales métodos:

  • Armonización de datos de NPS de más de 70 cohortes del Proyecto de Secuenciación de la Enfermedad de Alzheimer (ADSP) (>80 000 muestras).
  • Inclusión de datos de secuenciación del genoma completo del ADSP-FUS.
  • Definición y cálculo de clústeres de síntomas: psicosis/agitación temprana (EPA), psicosis/agitación tardía (LPA) y síntomas afectivos (AS), teniendo en cuenta las covariables.

Principales resultados:

  • Se completó la armonización de datos neuropsiquiátricos de 13 cohortes del ADSP (más de 30 000 individuos), con armonización en curso de cohortes diversas adicionales.
  • El análisis de datos de secuenciación del genoma completo está en curso.
  • Los análisis primarios identificarán nuevos factores de riesgo genético, caracterizarán la arquitectura genética compartida con trastornos psiquiátricos y evaluarán los efectos de la ascendencia.

Conclusiones:

  • La expansión del ADSP-FUS con fenotipos de NPS armonizados es crucial.
  • Los análisis propuestos proporcionarán una base para comprender los mecanismos moleculares de los NPS en poblaciones diversas de EA.
  • Esta investigación tiene como objetivo desentrañar la compleja etiología de los NPS perjudiciales en la EA.