Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer's Disease Brain

Rueli, Rachel H.; Parubrub, Arlene Condaya; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

doi:10.3233/jad-141755

Cited by 31 publications

(26 citation statements)

References 20 publications

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“…Moreover, patterns of Se species observed in serum of study subjects may not necessarily correspond to their distribution in other body districts and tissues, neither to what might be observed with very different types and amounts of Se exposure. In fact, laboratory and human studies have shown that relative distribution of Se species may differ according to the amount and type of dietary Se, as well as the body tissue and district under investigation and the disease status [51,57,[86][87][88][89][90][91], and even the correlation of the various Se species found in different compartments may vary greatly [20,51], thus highlighting the complexity of issues such as tissue-specific deposition and metabolism of the various Se species. Finally, it must be noted that, following ingestion of different Se species, retention of organic forms in body tissues is consistently higher than that of inorganic compounds [92], and therefore levels of Se species in serum (or other tissues) may not necessarily reflect the relative intake of these species through diet and other sources, nor their toxicity and biological effects [4,93].…”

Section: Discussionmentioning

confidence: 99%

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study

Vinceti

Grill

Malagoli

et al. 2015

Journal of Trace Elements in Medicine and Biology

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Section: Discussionmentioning

confidence: 99%

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study

Vinceti

Grill

Malagoli

et al. 2015

Journal of Trace Elements in Medicine and Biology

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“…We also consider it unlikely that such strongly increased selenium species levels were due to a compensatory response to a condition of oxidative stress, a mechanism which is well known to occur following environmental stressors including selenium itself [26] and which has been suggested to explain the excess selenoprotein P content in Alzheimer's disease brains [49]. In fact, in such a case we would have expected an increase limited to anti-oxidant selenium compounds, such as Se-GPx, Se-PP, and Se-TrxR, and not the other forms (such as Se-HSA and the inorganic ones, i.e., Se-IV and Se-VI) not belonging to the usual metabolic pathways for antioxidant selenoproteins synthesis in humans.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations

Mandrioli¹,

Michalke

Solovyev

et al. 2017

Neurodegener Dis

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Background: Although an increasing role of genetic susceptibility has been recognized, the role of environmental risk factors in amyotrophic lateral sclerosis (ALS) etiology is largely uncertain; among neurotoxic chemicals, epidemiological and biological plausibility has been provided for pesticides, the heavy metal lead, the metalloid selenium, and other persistent organic pollutants. Selenium involvement in ALS has been suggested on the basis of epidemiological studies, in vitro investigations, and veterinary studies in which selenium induced a selective toxicity against motor neurons. Objective: Hypothesizing a multistep pathogenic mechanism (genetic susceptibility and environmental exposure), we aimed to study selenium species in ALS patients carrying disease-associated gene mutations as compared to a series of hospital controls. Methods: Using advanced analytical techniques, we determined selenium species in cerebrospinal fluid sampled at diagnosis in 9 ALS patients carrying different gene mutations (C9ORF72, SOD1, FUS, TARDBP, ATXN2, and TUBA4A) compared to 42 controls. Results: In a patient with the tubulin-related TUBA4A mutation, we found highly elevated levels (in μg/L) of glutathione-peroxidase-bound selenium (32.8 vs. 1.0) as well as increased levels of selenoprotein-P-bound selenium (2.4 vs. 0.8), selenite (1.8 vs. 0.1), and selenate (0.9 vs. 0.1). In the remaining ALS patients, we detected elevated selenomethionine-bound selenium levels (0.38 vs. 0.06). Conclusions: Selenium compounds can impair tubulin synthesis and the cytoskeleton structure, as do tubulin-related gene mutations. The elevated selenium species levels in the TUBA4A patient may have a genetic etiology and/or represent a pathogenic pathway through which this mutation favors disease onset, though unmeasured confounding cannot be excluded. The elevated selenomethionine levels in the other patients are also of interest due to the toxicity of this nonphysiological selenium species. Our study is the first to assess selenium exposure in genetic ALS, suggesting an interaction between this environmental factor and genetics in triggering disease onset.

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“…Summary information of subjects was published previously [19]. 10 μm sections of medial temporal cortex were deparaffinized, and ‘antigen unmasking’ was achieved by heating to 95°C at 15 psi in a pressure cooker in an alkaline/EDTA solution (Trilogy, Cell Marque), followed by 3 min in 90% formic acid.…”

Section: Methodsmentioning

confidence: 99%

Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology

Rueli

Torres

Dewing

et al. 2016

JAD

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Previous studies demonstrated that selenium in the form of sodium selenate reduces neurofibrillary tangle formation in Alzheimer’s disease models. Hyperphosphorylation of tau, which leads to formation of neurofibrillary tangles in Alzheimer’s disease, is increased by endoplasmic reticulum (ER) stress. Selenoprotein S (SelS) is part of an ER membrane complex that removes misfolded proteins from the ER as a means to reduce ER stress. Selenate, as with other forms of selenium, will increase selenoprotein expression. We therefore proposed that increased SelS expression by selenate would contribute to the beneficial actions of selenate in Alzheimer’s disease. SelS expression increased with ER stress and decreased under conditions of elevated glucose concentrations in the SH-SY5Y neuronal cell line. Reducing expression of SelS with siRNA promoted cell death in response to ER stress. Selenate increased SelS expression, which significantly correlated with decreased tau phosphorylation. Restricting SelS expression during ER stress conditions increased tau phosphorylation, and also promoted aggregation of phosphorylated tau in neurites and soma. In human postmortem brain, SelS expression coincided with neurofibrillary tangles, but not with amyloid-β plaques. These results indicate that selenate can alter phosphorylation of tau by increasing expression of SelS in Alzheimer’s disease and potentially other neurodegenerative disorders.

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Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer's Disease Brain

Cited by 31 publications

References 20 publications

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study

Elevated Levels of Selenium Species in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients with Disease-Associated Gene Mutations

Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology

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