Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

Council for Nutritional and Environmental Medicine Mo i Rana Norway

Department of Clinical Physiology St Goran Hospital Stockholm Sweden

Department of Neurology and Center of Clinical Neuroscience Charles University Prague 1st Faculty of Medicine and General University Hospital Prague Prague Czech Republic

Department of Public Health Hedmark University of Applied Sciences Elverum Norway

Department of Research Innlandet Hospital Trust Brumunddal Norway

Division of Cardiovascular Medicine Department of Medical and Health Sciences Linköping University Linköping Sweden

Institute of Environmental Medicine IMM Karolinska Institutet Nobels väg 13 Box 210 17177 Stockholm Sweden

Norwegian Institute of Public Health Oslo Norway

Norwegian University of Life Sciences Ås Norway

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A Summary of New Findings on the Biological Effects of Selenium in Selected Animal Species-A Critical Review