Search

Abstract The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid- beta and hyperphosphorylated tau-protein). Graphical abstract fx1 Highlights • Se is crucial to the brain; its deprivation causes irreversible damage to neuronal tissue. • SELENOP delivers Se to the brain by binding to a surface receptor, ApoER2. • SELENOP is strongly linked to hallmarks of AD (A β plaques and neurofibrillary tangles). • Studies indicate a beneficial effect of Se and SELENOP in cognition and AD pathology. • SELENOP binds redox-active metals in the brain, providing neuroprotection. [ABSTRACT FROM AUTHOR]