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Elizabeth Ochoa1, Savannah Barannikov1, Mallory Keating2

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Alzheimer's & dementia : the journal of the Alzheimer's Association
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PubMed
Resumen
Este resumen es generado por máquina.

Las personas hispanas enfrentan un mayor riesgo de demencia. Este estudio analizó la expresión génica en sus cerebros, encontrando patrones únicos en la enfermedad de Alzheimer (EA) y la enfermedad cerebrovascular (ECV) que pueden informar la medicina de precisión.

Palabras clave:
neuroinflamacióndemenciaascendencia hispanamedicina de precisiónexpresión génicaenfermedad de Alzheimerenfermedad cerebrovascular

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Área de la Ciencia:

  • Neurociencia; Genética; Patología

Sus antecedentes:

  • Las personas hispanas tienen un riesgo 1,5 veces mayor de padecer la enfermedad de Alzheimer y demencias relacionadas, pero están subrepresentadas en la investigación.
  • Estudios previos sugieren una carga alterada de la patología de Alzheimer y una modificación de la expresión génica relacionada con la ascendencia en poblaciones hispanas.
  • Pocos estudios han investigado la expresión génica diferencial en la demencia utilizando tejido cerebral post mortem de descendientes hispanos.

Objetivo del estudio:

  • Investigar la expresión génica neuroinflamatoria en el tejido cerebral post mortem de descendientes hispanos con demencia.
  • Identificar perfiles transcripcionales específicos de la ascendencia y la etiología en la demencia.
  • Sentar las bases para enfoques de medicina de precisión en la atención de la demencia para poblaciones en riesgo y subrepresentadas.

Principales métodos:

  • Se extrajo ARN de la corteza frontal del tejido cerebral post mortem de descendientes hispanos y no hispanos con enfermedad de Alzheimer (EA), enfermedad cerebrovascular (ECV) o etiología mixta (ECVA).
  • La expresión génica se cuantificó utilizando el panel de neuroinflamación humana NanoString y la tecnología SPRINT nCounter.
  • El análisis siguió los criterios de análisis avanzado de NanoString, excluyendo genes de bajo recuento y de fondo.

Principales resultados:

  • Se observó un enriquecimiento compartido de vías de la categoría de genes de la Función Astroctiaria al comparar descendientes hispanos con EA o ECVA con descendientes no hispanos.
  • Se expresaron diferencialmente dos genes en la EA hispana y siete en la ECVA hispana en comparación con los descendientes no hispanos.
  • Los genes P2RY12, NRP2 y PRKACB, entre otros, mostraron niveles de transcripción elevados en la corteza frontal de descendientes hispanos con ECV en comparación con otras etiologías.

Conclusiones:

  • Los hallazgos preliminares sugieren perfiles transcripcionales distintos en la enfermedad cerebrovascular (ECV) influenciados por la ascendencia y la etiología.
  • La ascendencia parece modificar un número limitado de genes en la enfermedad de Alzheimer (EA) y la demencia de etiología mixta (ECVA).
  • Investigaciones futuras examinarán la expresión génica diferencial en relación con la patología y desarrollarán modelos genéticos funcionales para identificar genes específicos de la ascendencia hispana y la enfermedad para la atención de precisión de la demencia.