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EVALUAN EL EFECTO DE LAS ESTATINAS SOBRE LA PRODUCCION DE Β-AMILOIDE

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A pesar de su notable efecto sobre el metabolismo del colesterol, el tratamiento con estatinas, dentro de su intervalo terapéutico, no parece asociarse con modificación significativa de la concentración de β-amiloide en personas con hipercolesterolemia o enfermedad de Alzheimer. En consecuencia, en dosis clínicamente útiles, las estatinas podrían carecer de repercusión sobre la producción o segregación de β-amiloide, según propone la estrategia actualmente debatida para detener la progresión de la enfermedad de Alzheimer. Otros efectos de las estatinas pueden ser responsables de su acción protectora contra la demencia.
hoglund9.jpg Autor:
Kina Höglund
Columnista Experto de SIIC

Institución:
Göteborg University

Artículos publicados por Kina Höglund
Coautor
Kaj Blennow* 
MD, PhD, Göteborg University, Mölndal, Suecia*
Recepción del artículo
5 de Septiembre, 2006 		Aprobación
13 de Septiembre, 2006
Primera edición
14 de Diciembre, 2006 		Segunda edición, ampliada y corregida
7 de Junio, 2021

EVALUAN EL EFECTO DE LAS ESTATINAS SOBRE LA PRODUCCION DE Β-AMILOIDE

Resumen
Hasta la fecha, se formularon numerosas hipótesis en un intento por establecer la causa de la enfermedad de Alzheimer (EA), la forma más frecuente de demencia. Aquella que considera el papel del colesterol, basada principalmente en estudios en cultivos celulares y en animales, afirma que los niveles aumentados de colesterol inducen la vía amiloidogénica durante el metabolismo de la proteína precursora de amiloide (PPA) y, en consecuencia, promueven la producción del péptido beta amiloide (βA), principal constituyente de las placas seniles. Representa una teoría ampliamente aceptada que la adición de βA en las placas es un evento inicial en la EA, el cual resulta en neurodegeneración. La presente revisión se centra en la hipótesis del colesterol y su aplicación a los seres humanos. Se revisa y discute el papel del tratamiento para reducir los niveles de colesterol con estatinas.

Palabras clave
enfermedad de Alzheimer, colesterol, estatinas, ß-amiloide, líquido cefalorraquídeo


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STATIN-INDUCED REDUCTION OF ß-AMYLOID PRODUCTION IN ALZHEIMER'S DISEASE

Abstract
To date a number of hypotheses have been postulated trying to state the cause of Alzheimer's disease (AD), the most common form of dementia. The cholesterol hypothesis, based primarily on cell- and animal studies, states that increased levels of cholesterol induces the amyloidogenic pathway of the processing of the amyloid precursor protein (APP), thereby promoting production of the ß-amyloid peptide(Aß). The Aß peptide is the major constituent of senile plaques, which together with atrophy and neurofibrillary tangles is the main neuropathological finding in AD. It is a widely accepted theory that aggregation of Aß into plaques is a initial event in AD, driving neurodegeneration. This review focuses on the cholesterol hypothesis and its implementation on human beings. The role of cholesterol lowering treatment using statins is reviewed and discussed.

Key words
cholesterol, statins, B-amyloid, CSF, Alzheimer's disease


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Especialidades
Principal: Bioquímica
Relacionadas: Anatomía Patológica, Cardiología, Farmacología, Geriatría, Medicina Farmacéutica, Medicina Interna, Neurología, Toxicología



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Kina Höglund, Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, Neurochemistrylab, Göteborg University, S-431080, Mölndal, Suecia
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