REVIEW ARTICLE Selenoprotein P and its potential role in Alzheimer’s disease Nikolay Solovyev 1,2 Received: 20 February 2019 /Accepted: 29 May 2019 # Hellenic Endocrine Society 2019 Abstract Alzheimer’ s disease (AD) is the most common neurodegenerative disease associated with cognitive decline, loss of memory, and progressive cerebral atrophy. The trace element selenium (Se) is known to be involved in brain pathology. Selenoprotein P (SELENOP), as the main Se transport protein, is, to a great extent, responsible for maintaining Se homeostasis and the hierarchy of selenoprotein expression in the body. Adequate Se supply through SELENOP is vital for proper brain development and function. Additionally, SELENOP may be implicated in pathological processes in the central nervous system, including those in AD. The current review summarizes recent findings on the possible role of SELENOP in AD, with a focus on probable mechanisms: Se delivery to neurons, antioxidant activity, cytoskeleton assembly, interaction with redox-active metals (e.g., copper and iron), and misfolded proteins (amyloid beta and tau protein). The use of SELENOP as a biomarker of Se status is also briefly discussed. Epidemiological studies on Se supplementation are beyond the scope of the current review. Keywords Alzheimer’ s disease . Selenium . Selenoprotein P . Brain . Oxidative stress . Redox regulation . Biomarkers . Trace elements Introduction Alzheimer’ s disease (AD) is the most common neurodegener- ative disease and the most common cause of dementia world- wide. Progressive cerebral atrophy (death of brain cells) causes cognitive decline, memory deficits, and in some cases severe personality disorders [1]. The etiology of AD still remains un- der debate, with the so-called amyloid theory [2–4] being cur- rently the most widely accepted [5]. The accumulation of pro- tein aggregates of amyloid-β and hyperphosphorylated tau causes neuronal cell death and synaptic malfunction. Since there is yet no clarity around the causation of these pathologic events, environmental factors are widely considered as possible risk factors in AD and other neurodegenerative processes [6]. Inorganic elements such as aluminum, transition metals, cop- per, iron, zinc, and metalloid selenium (Se) are considered as pathogenetic factors for AD [7]. Selenoprotein P (Selenop) is one of 25 human selenoproteins [8], a highly specialized group of proteins con- taining selenocysteine (Sec), a Se analog of amino acid cyste- ine (Cys). SELENOP seems to be a multifunctional protein [9], with body Se transport being considered a main function [10]. In humans, SELENOP contains up to 10 Se atoms as Sec residues [11, 12]. Se is an essential trace element for the hu- man brain, but it also can be highly neurotoxic, depending on intake and speciation [12–14]. The human body is known to maintain a strict hierarchy for Se distribution and selenoprotein expression [15]. The brain ranks high in this hierarchy and is able to restrict Se supply from other tissues in the event of inadequate dietary intake of this trace element [16–18]. Selenoproteins, and most importantly glutathione peroxidases (GPX) types I–VI and VI (GPX1–4, GPX6), thioredoxin reductases type I–III, and methionine sulfoxide reductase B1, as well as inter alia, SELENOP, and selenoprotein W, exhibit reductive enzymatic activity [19], counteracting oxidative stress, an important molecular mech- anism of neurodegeneration [20]. Recently, Ingold et al. [22] demonstrated that the substitution of Sec for its sulfur analog Cys in GPX4 (Gpx4 Cys/Cys), an essential selenoprotein for neurons and proper prenatal development [21], preserves at least partial activity and is sufficient for embryonic develop- ment. However, the presence of Sec, i.e., Se, in GPX4 was found to be crucial for postnatal development, preventing * Nikolay Solovyev n.solovyev@spbu.ru; nikolay.solovyev@ugent.be 1 Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, Russian Federation 199034 2 Department of Chemistry, Atomic & Mass Spectrometry – A&MS Research Unit, Ghent University, Campus Sterre, Krijgslaan, 281-S12, 9000 Ghent, Belgium Hormones https://doi.org/10.1007/s42000-019-00112-w