Selenium In Cerebrospinal Fluid Research Articles

Association between metals and metalloids with cognitive status in Mild Cognitive Impairment subjects

Abstract Mild Cognitive Impairment (MCI) is regarded as a transitional state between normal aging and dementia. Several risk factors have been related to MCI and dementia vulnerability. Among these, metals and metalloids have been hypothesized to affect dementia risk. Our objective was to study the associations between metals and metalloids (cadmium, copper, iron, manganese, selenium, zinc) concentrations in serum and cerebrospinal fluid (CSF) with cognitive impairment status of MCI subjects. 144 individuals newly diagnosed with MCI were recruited at Neurology Memory Clinics at Modena and Reggio Emilia Hospitals (Italy) in the period 2019-2022. The concentrations of elements in paired serum/CSF were determined using inductively coupled plasma mass spectrometry. Participants’ global cognitive status was assessed using the Mini-Mental State Examination (MMSE). Muti-adjusted spline regression analyses were performed to assess the relation between the serum/CSF concentrations and MMSE. Median serum and CSF concentrations were generally higher in men than women, except copper in serum and iron in CSF demonstrating higher concentrations in women. A positive linear association emerged between serum iron concentrations and MMSE, while a slight negative one emerged for serum selenium levels. Cadmium in serum was positively associated with MMSE until 0.2 µg/L and then the association became null, while in CSF a U-shaped relation emerged. A U-shaped relation was also observed for serum copper and CSF iron and manganese levels. CSF selenium concentrations were inversely related to MMSE, although above 5 µg/L the curve flattened. Zinc exhibited the same pattern of association in both serum and CSF, i.e., an inverted U-shaped one. These findings suggest that CSF and serum content of the investigated elements may be differently related with global cognitive status in MCI subjects. Higher levels of selenium and zinc, in particular, are associated with lower MMSE score. Key messages • Heavy metals and metalloids display different pattern of association with global cognitive status. • High levels of selenium and zinc are inversely related with global cognitive status in MCI subjects.

Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer's Disease.

Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32mg sodium selenate, 3 times daily), or supranutritional (10mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au /), ID: ACTRN12611001200976.

A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I)

BackgroundAvailable studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AimThe objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. MethodsAll major databases were searched for eligible studies. We included 12 case–control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. ResultsRandom-effects meta-analysis indicated a decrease in circulatory (SMD=−0.44), erythrocellular (SMD=−0.52) and CSF (SMD=−0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=−0.55) and without (SMD=−0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. ConclusionThis meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD.

Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite

Exposure to selenium, and particularly to its inorganic forms, has been hypothesized as a risk factor for amyotrophic lateral sclerosis (ALS), a fast progressing motor neuron disease with poorly understood etiology. However, no information is known about levels of inorganic and some organic selenium species in the central nervous system of ALS patients, and recent observations suggest that peripheral biomarkers of exposure are unable to predict these levels for several Se species including the inorganic forms. Using a hospital-referred case–control series and advanced selenium speciation methods, we compared the chemical species of selenium in cerebrospinal fluid from 38 ALS patients to those of 38 reference neurological patients matched on age and gender. We found that higher concentrations of inorganic selenium in the form of selenite and of human serum albumin-bound selenium were associated with increased ALS risk (relative risks 3.9 (95% confidence interval 1.2–11.0) and 1.7 (1.0–2.9) for 0.1μg/L increase). Conversely, lower concentrations of selenoprotein P-bound selenium were associated with increased risk (relative risk 0.2 for 1μg/L increase, 95% confidence interval 0.04–0.8). The associations were stronger among cases age 50 years or older, who are postulated to have lower rates of genetic disease origin. These results suggest that excess selenite and human serum albumin bound-selenium and low levels of selenoprotein P-bound selenium in the central nervous system, which may be related, may play a role in ALS etiology.

Cerebrospinal fluid selenium and chromium levels in patients with Parkinson's disease.

We compared CSF and serum levels of selenium and chromium, measured by atomic absorption spectrophotometry, in 28 patients with Parkinson's disease (PD) and 43 matched controls. The CSF and serum levels of these trace metals did not differ significantly between PD patients and controls. CSF selenium and chromium levels were not correlated with age, age at onset, duration of the disease, scores of the Unified Parkinson Disease Rating Scale of the Hoehn and Yahr staging in the PD group. Although antiparkinsonian therapy did not influence significantly the CSF levels of selenium, PD patients not treated with levodopa had significantly higher CSF selenium levels than controls (p < 0.01). It is possible that increased CSF selenium levels could indicate an attempt of protection against oxidative stress. The normality of CSF and serum chromium levels suggest that these values are not related with the risk for PD.

Trace elements in cerebrospinal fluid in motor neurone disease.

Concentrations of sodium, chlorine, potassium, chromium, iron, cobalt, zinc, rubidium, silver, caesium, and selenium in cerebrospinal fluid from 14 control subjects and 20 patients with motor neurone disease were measured by in vitro neutron activation analysis. No statistically significant correlation was found between the concentrations of any two elements other than sodium and chlorine in either the patient or control group (r = 0.9905; p less than 0.001). The mean cobalt concentration was significantly lower in the patients (p = 0.0015). No other statistically significant difference was shown. The relevance of this finding was examined in relation to current concepts of the pathogenesis of motor neurone disease and the role of cobalt in cellular metabolism.