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

Artículo completo
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.

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