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The Complex Actions of Statins in Brain and their Relevance for Alzheimer’s Disease Treatment: An Analytical Review

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In view that several studies have shown a positive correlation between high cholesterol and an increase in the risk for developing Alzheimer’s disease (AD) statins have been proposed as alternative drugs for its treatment and/or prevention. However, the potential benefits of statins remain controversial. Although they have lipid-lowering properties, statins also have pleiotropic effects that are unrelated to cholesterol reduction and have a wide range of biological implications whose consequences in brain function have not been fully characterized. In this work we analyze different studies that have reported both, beneficial and toxic effects for statins in the central nervous system (CNS), and we revise the literature that claims their potential for treating AD. First, we present an overview of the cholesterol metabolism and its regulation in the brain in order to provide the framework for understanding the pathological association between altered cholesterol and AD. Then, we describe the cholesterol-lowering and pleiotropic properties of statins that have been reported in vivo and in in vitro models. We conclude that the effects of statins in the brain are broad and complex and that their use for treating several diseases including AD should be carefully analyzed given their multiple and broad effects.
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Keywords: Alzheimer's disease; HMG-CoA reductase; amyloid beta; cholesterol pathway; isoprenoids; neuroprotection; neurotoxicity; statins

Document Type: Research Article

Publication date: November 1, 2014

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  • Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.
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