La ApoE-e4 favorece mayor acumulación de beta-amiloide

La tontería es infinitamente más fascinante que la inteligencia. La inteligencia tiene sus limites, la tontería no

Claude Chabrol

 Un estudio que se publica hoy en Science Translational Medicine muestra que la isoforma e4 de la ApoE es la que mayor riesgo de acumulación de beta-amiloide tiene, por lo que aumenta el riesgo en los portadores de desarrollar enfermedad de Alzheimer.Un nuevo estudio podría ayudar a explicar por qué la proteína beta-amiloide, propia de la enfermedad de Alzheimer, se acumula en los cerebros de algunas personas más que en los de otras. Los hallazgos podrían conducir a nuevas maneras para retrasar o incluso detener la acumulación de placas amiloides en pacientes.

El equipo de David Holtzman, de la Universidad Washington en Saint Louis, ha identificado varios genes que parecen incrementar el riesgo de Alzheimer, aunque el gen ApoE y su proteína son aún el factor más importante para desarrollar la enfermedad. Los resultados del estudio se publican hoy en Science Translational Medicine.

La ApoE-e4 es una de las tres formas comunes de proteína del gen ApoE (las otras son ApoE-e2 y ApoE-e3). Estudios previos han mostrado que la ApoE-4 ayuda a dirigir la acumulación de proteínas beta-amiloide, que se agrupan para formar placas amiloides en los cerebros de pacientes con Alzheimer.

En el citado estudio, Holtzman demuestra que la ApoE-4 contribuye a la acumulación de beta-amiloide mediante la desaceleración de su aclaramiento del cerebro.

Primero, los autores se fijaron en la concentración beta-amiloide en el líquido cefalorraquideo de individuos cognitivamente normales de menos de 70 años de edad que eran portadores de formas distintas de ApoE.

El equipo ha descubierto que los individuos con ApoE-e4 tenían mucha más proteína beta-amiloide en el cerebro que aquéllos con las formas ApoE-e2 y ApoE-e3. Con la técnica de microdiálisis, los investigadores han observado las concentraciones de beta-amiloide en ratones genéticamente modificados para expresar todas las formas de proteína humana de ApoE.

Han visto mayores concentraciones de beta-amiloide en los animales que expresan la ApoE-e4 humana que en los que expresan las formas E3 y E2 de la proteína. De manera destacada, el equipo también ha descubierto que en los ratones, tanto jóvenes como viejos, con la ApoE-e4 humana la beta-amiloide se aclaró en su cerebro mucho más lentamente que en aquéllos con las otras formas de la proteína. Los resultados muestran que la ApoE-e4 provoca la acumulación de beta-amiloide y mayor riesgo de Alzheimer.

(Science Translational Medicine 2011; 89 89ra57).

Fuente:www.diariomedico.com

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