Combination of neurofilament heavy chain and complement C3 as CSF biomarkers for ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease with an average survival of 3 years from symptom onset. Rapid and conclusive early diagnosis is essential if interventions with disease-modifying therapies are to be successful. Cytoskeletal modification and inflammation are known to occur during the pathogenesis of ALS. We measured levels of cytoskeletal proteins and inflammatory markers in the CSF of ALS, disease controls and healthy subjects. We determined threshold values for each protein that provided the optimal sensitivity and specificity for ALS within a training set, as determined by receiver operating characteristic analysis. Interestingly, the optimal assay was a ratio of the levels for phosphorylated neurofilament heavy chain and complement C3 (pNFH/C3). We next applied this assay to a separate test set of CSF samples to verify our results. Overall, the predictive pNFH/C3 ratio identified ALS with 87.3% sensitivity and 94.6% specificity in a total of 71 ALS subjects, 52 disease control subjects and 40 healthy subjects. In addition, the level of CSF pNFH correlated with survival of ALS patients. We also detected increased pNFH in the plasma of ALS patients and observed a correlation between CSF and plasma pNFH levels within the same subjects. These findings support large-scale prospective biomarker studies to determine the clinical utility of diagnostic and prognostic signatures in ALS.     

Transforming growth factor-Beta 1 (tgf-Beta 1) in patients with amyotrophic lateral sclerosis

Previous investigations have shown that the transforming growth factor-beta 1 (TGF-beta 1) may protect neurons against excitotoxic and oxidative damage and may inhibit apoptosis. The aim of this study was to investigate the role of TGF-beta 1 in patients with amyotrophic lateral sclerosis (ALS). The study involved 24 ALS patients and 15 control group people. The ALS patients were divided into groups according to their clinical status, and duration of ALS. The TGF-beta 1 in the serum and cerebrospinal fluid (CSF) was measured by the enzyme-linked immunosorbent assay (ELISA). Results showed that TGF-beta 1 concentrations in the serum, and CSF in the whole group of ALS patients did not differ from those of the controls, but the serum TGF-beta 1 concentration was significantly higher in ALS patients with a terminal clinical status than in controls. The TGF-beta 1 concentration was significantly higher in the CSF of the patients, with a long duration of ALS, than in the patients with a short duration of ALS, and there was a significant positive correlation between the CSF TGF-beta 1 and the duration of ALS. TGF-beta 1 may play a role in neurodegeneration of ALS, and may be an indicator of the duration of the disease.     

Analysis of smoking and LPO in ALS

Smoking has been suggested as one of the risk factor for amyotrophic lateral sclerosis (ALS) development. In order to investigate whether adverse effects of cigarette smoke in ALS have any association with increase in oxidative stress, disease severity, lipid hydroperoxides (LPO) and superoxide dismutase-1 (SOD1) levels were measured in biofluids of smoker and never smoker ALS patients and clinically correlated. Serum and CSF from sporadic ALS patients (n = 50) diagnosed with El Escorial criteria were collected in the study. Serum (n = 50) and CSF (n = 42) were also collected from normal healthy controls. The LPO levels were estimated using commercially available kits. Enzyme-linked immunosorbent assays (ELISAs) were used to quantitate SOD1. Their levels were further analyzed among smoker and never smoker subjects. Significantly elevated LPO in sera and CSF of ALS patients were observed (p < 0.05). There was considerably increased LPO in sera and CSF of smoker ALS subjects matched with disease severity as compared to never smoker ALS (p < 0.05). ALS group did not show any alteration in SOD1 when compared to controls (p > 0.05). In addition, no change has been observed in SOD1 levels in ALS subjects who smoke (p > 0.05). Increased LPO and unaltered SOD1 in ALS patients may suggest the neuro-pathological association of LPO with ALS disease independent of SOD1. With current findings, it may be proposed that LPO levels might constitute as probable biomarker for smoker ALS patients, however, it cannot be concluded without larger gender matched studies. Additional investigations are needed to determine whether LPO upregulation is primary or secondary to motor neuron degeneration in ALS.     

Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n?=?17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.     

Teniasis

The aim of this study was to investigate the changes of level of the essential elements of copper, magnesium, and zinc status in cases of teniasis in children. Copper, magnesium, and zinc levels were measured in 40 children who were positive for intestinal parasite of Taenia saginata. Scores were obtained for the positives and their 30 age- and sex-matched T. saginata-negative healthy children. The mean concentration of copper, magnesium, and zinc in blood showed no statistically difference in T. saginata-positive children than in their controls both in females (p>0.05) and males (p>0.05). However, a clear numerically decrease was observed especially in magnesium and zinc levels compared to the controls both in females and males. The average magnesium concentration in T. saginata-positive female children and male children were 20±1.9 and 22±2.2 mg/L and it was 27±2.1 and 27±2.3 mg/L in controls, respectively. The mean values of the zinc in blood were 0.76±0.5 and 0.72±0.4 mg/L in T. saginata-positive female children and male children and 0.85±0.3 and 0.81±0.5 mg/L in female and male controls, respectively. No correlation could be demonstrated between age and mean values of copper, magnesium, and zinc in T. saginata-positive females and males and controls (p>0.05). No significant correlation could be found between blood copper, magnesium and zinc levels in T. saginata-positive female and male children and controls (p>0.05). Although there was no statistical correlation observed in copper, magnesium, and zinc levels between patients and controls, there seem to be, especially in magnesium and zinc levels, a decrease, whereas no change was seen in the zinc level in children infected with T. saginata compared to controls.     

Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia

In the present study, the serum and hair levels of zinc, selenium, and copper were determined in children with iron-deficiency anemia (IDA). A total of 52 anemic children aged 1–4 yr constituted the study group. Fortysix healthy children acted as controls. The copper and zinc levels were measured with an atomic absorption spectrophometer. Serum and hair selenium was determined by a spectroflourometric method. The serum zinc and selenium concentrations in the IDA group were found to be significantly lower and serum copper significantly higher than those in the controls (p<0.05). Lower iron, zinc, and selenium concentrations (p<0.001) but not copper were found in hair (p>0.05).     

Comparative Study of Serum Zinc, Copper, Manganese, and Iron in Preeclamptic Pregnant Women

Preeclampsia complicates 2–8 % of all pregnancies and it is one of the leading causes of maternal mortality and pre-term delivery in the world. Unfortunately, there is scarcity of document discussing the circulating level of several essential trace elements in preeclampsia patients in Bangladesh. The present study was designed to evaluate the serum concentration of four trace elements, namely zinc, copper, manganese, and iron, in preeclamptic pregnant women. The study was conducted as a case–control study with 50 preeclamptic pregnant women as cases and 58 normotensive pregnant women as controls. Obstetric, anthropometric, and clinical data were collected at routine obstetric visits. Serum trace elements were determined by flame atomic absorption spectroscopy. Independent sample t test and Pearson’s correlation test were done for the statistical analysis using the statistical software package SPSS, version 16.0 (SPSS Inc., Chicago, IL). We observed significant differences for gestational age, body mass index, and systolic and diastolic blood pressure between patient and control groups (p?<?0.05). Analysis of serum trace elements explored significantly lower level of all the four elements in preeclampsia patients in comparison to the control group (p?<?0.05). Pearson’s correlation analysis explored that the correlation between serum level of different trace elements was statistically insignificant (p?>?0.05) except the correlation between zinc and iron in preeclampsia patients (p?<?0.05). Establishment of inter-element relationship strongly supports that there was a disturbance in the element homeostasis in patient with preeclampsia. In conclusion, our study suggests that preeclampsia patients have considerably lower level of serum zinc, copper, manganese, and iron compared to the healthy pregnant women.     

Erythropoietin in Cerebrospinal Fluid: Age-related Reference Values and Relevance in Neurological Disease

We aimed to establish age-related reference values for Erythropoietin (EPO) in cerebrospinal fluid (CSF) and to evaluate concentrations in neurological diseases. CSF and serum EPO was measured in controls with tension-type headache (CTTH), in patients with ALS, dementia and depression using ELISA technique. Stability experiments showed CSF EPO to be stable for two and a half months and over two thaw/freeze cycles. A positive correlation of CSF EPO with age was found (P < 0.01). We found a CSF/serum EPO concentration ratio of 0.126, pointing towards an intrathecal synthesis of EPO. The ALS group showed significantly lowered CSF EPO compared to age-matched CTTH (P < 0.012), whereas the dementia and depression group showed no significant differences compared to CTTH. The establishment of age-related reference values in a large cohort of controls will improve the interpretation of future CSF EPO evaluations in neurological diseases. The authors have not reported any conflicts of interest.     

Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia

In order to evaluate serum copper and zinc status in children with iron deficiency anemia (IDA), 60 children with IDA aged 1–14 yr and 64 healthy children as controls aged 1–14 yr were included the study. Serum copper levels were higher in children with IDA (189 ± 49 (Μg/dL) than those of controls (163 ± 37 Μg/dL) (p = 0.001). Serum zinc levels were lower in the patient group (109 ± 59 Μg/dL) than those of control subjects (135 ± 56 Μg/dL) (p = 0.017). In addition, there were statistically significant negative correlations between hematological parameters and serum copper levels in the patient group, but not in controls. No correlation between hematological parameters and serum zinc levels were found in both patient and control groups, except positive correlation between mean corpuscular volume (MCV) and serum zinc level in patients. It was concluded that at the time of managing children with IDA, zinc deficiency must be borne in mind and if necessary treatment should be initiated with zinc.     

Neurofilament markers in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis

This study aims to determine the serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) in amyotrophic lateral sclerosis (ALS) patients, and to explore their feasibility as valid biomarkers for quantifying disease progression and predicting individual prognosis. 52 patients with ALS and 30 controls with noninflammatory neurological diseases were included. NFL and pNFH levels in serum and CSF were measured by enzyme‐linked immunosorbent assay. Our findings showed that serum and CSF levels of NFL and pNFH in ALS patients were significantly increased. These values were negatively correlated with disease duration (except CSF NFL with disease duration) and ALSFRS‐r score, and positively correlated with disease progression rate (DPR) and upper motor neuron (UMN) score, but did not correlate with bilateral median and ulnar nerve compound muscle action potential (cMAP) amplitudes (except a weak correlation between CSF NFL and cMAP amplitudes). The optimal cut‐off values with high sensitivity and specificity were obtained in ROC curve analysis to discriminate ALS from controls. Kaplan‐Meier survival curves illustrated that survival was significantly shorter for patients with higher neurofilament levels at diagnosis. The Cox proportional hazards regressions confirmed that NFL and pNFH were significant predictors of survival. Overall, NFL and pNFH in serum and CSF can be used as reliable biomarkers in ALS.     

Angiogenin levels and ANG genotypes: dysregulation in amyotrophic lateral sclerosis

Objective

To determine whether 5 single nucleotide polymorphisms (SNPs) associate with ALS in 3 different populations. We also assessed the contribution of genotype to angiogenin levels in plasma and CSF.

Methods

Allelic association statistics were calculated for polymorphisms in the ANG gene in 859 patients and 1047 controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin levels were quantified and stratified according to genotypes across the ANG gene. The contribution of SNP genotypes to variance in circulating angiogenin levels was estimated in patients and controls.

Results

All SNPs showed association with ALS in the Irish group. The SNP rs17114699 replicated in the Swedish cohort. No SNP associated in the Polish cohort. Age- and sex-corrected circulating angiogenin levels were significantly lower in patients than in controls (p<0.001). An allele dose-dependent regulation of angiogenin levels was observed in controls. This regulation was attenuated in the ALS cohort. A significant positive correlation between CSF plasma angiogenin levels was present in controls and abolished in ALS.

Conclusions

ANG variants associate with ALS in the Irish and Swedish populations, but not in the Polish. There is evidence of dysregulation of angiogenin expression in plasma and CSF in sporadic ALS. Angiogenin expression is likely to be important in the pathogenesis of ALS.     

Metal concentrations in cerebrospinal fluid,blood, serum,plasma, hair,and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10–15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients.PurposeThis meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients.MethodsWe searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison.FindingsTwenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83–4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 – 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 – 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups.ConclusionLead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.     

A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients

The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.     

Cystatin C: a candidate biomarker for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA) to assess initial and longitudinal cerebrospinal fluid (CSF) and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival.     

Proteome Analysis of Cerebrospinal Fluid in Amyotrophic Lateral Sclerosis (ALS)

Cerebrospinal fluid (CSF) is a promising source of biomarkers in amyotrophic lateral sclerosis (ALS). Using the two-dimensional difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS (n = 14) with those from normal controls (n = 14). Protein spots that showed significant differences between patients and controls were selected for further analysis by MALDI-TOF mass spectrometry. For validation of identified spots western blot analysis and ELISA was performed. We identified 2 proteins that were upregulated and 3 proteins that were down-regulated in CSF in ALS. Of these, two proteins (Zn-alpha-2-glycoprotein and ceruloplasmin precursor protein) have not been reported in CSF of patients with ALS so far. In contrast, several other proteins (transferrin, alpha-1-antitrypsin precursor and beta-2-microglobulin) seem to be unspecifically affected in different neurological diseases and may therefore be of limited value as disease-related biochemical markers in ALS. Further evaluation of the candidate proteins identified here is necessary.     

Serum, zinc, copper and insulin in diabetes mellitus

We studied serum zinc, copper, ceruloplasmin, insulin, basal glycemia and cholesterol in 49 diabetics on oral anti-diabetic agent and in 10 normal people. We found there is an elevation of serum zinc, copper and ceruloplasmin in the diabetic group that is statistically significant (p less than 0.001). There is a significant correlation between zinc and insulin (p less than 0.001), and between the quotient zinc/copper and cholesterol (p less than 0.001). The increase of plasma zinc can reflect a deficient storage or a chronic hypersecretion of insulin in hyperglucemic patients. We think that the quotient zinc/copper/might play a role in the pathogenesis of the arteriosclerosis in diabetes.     

Plasma Trace Elements, Vitamin B12, Folate, and Homocysteine Levels in Cirrhotic Patients Compared to Healthy Controls

Increased serum homocysteine (Hcy) can induce liver diseases and can play a remarkable role in hepatic disorders. The purpose of the present study therefore was to investigate the relationship between serum vitamin B(12), folate, zinc and copper, cysteine, and Hcy level differences between cirrhotic patients and healthy subjects. We studied 32 cirrhotic patients (12 females and 20 males) aged 45 +/- 11 years and 32 control subjects (12 females and 20 males) aged 39 +/- 9 years. There was an inverse correlation between Hcy and vitamin B(12) in controls (r = -0.442, p < 0.011) but not in cirrhotic patients (r = -0.147, not significant). Also, mean plasma folate was decreased in cirrhotic patients compared to controls (p < 0.001). Copper increased whereas zinc decreased significantly in cirrhotic patients. A positive correlation was seen between the Cu/Zn ratio and Cu in controls (r = 0.690, p < 0.01), but the correlation between the Cu/Zn ratio and Cu was not significant in the cirrhotic group. Negative correlations were seen between plasma concentration of zinc and the Cu/Zn ratio in controls and cirrhotic patients (r = -0.618, p < 0.01 and r = -0.670, p < 0.01, respectively). Cirrhotic patients displayed multiple abnormalities, including changes in cysteine metabolism and in zinc and copper levels. Although hyperhomocysteinemia is known as an atherogenic and thrombogenic risk factor for cardiovascular disease, it might also be a risk factor for cirrhotic patients. Plasma Hcy, vitamin B(12), and folic acid measurement may be useful in the evaluation of cirrhotic patients.     

Diagnostic and prognostic value of CSF neurofilaments in a cohort of patients with motor neuron disease: A cross-sectional study

Motor neuron disease (MND) is a rare group of disorders characterized by degeneration of motor neurons (MNs). The most common form of MND, amyotrophic lateral sclerosis (ALS), is an incurable disease with a variable rate of progression. The search of robust biomarkers able to discriminate among different ALS forms is paramount to properly stratify patients, and to identify those who could most likely benefit from experimental therapies. Phosphorylated-neurofilament heavy chain (p-NfH) and neurofilament light chain (NfL) are neuron-specific components of the cytoskeleton and may represent reliable markers of neuronal injury in neurological disorders. In this study, we described our cohort of ALS patients in order to investigate whether and how cerebrospinal fluid (CSF) p-NfH and NfL levels may reflect progression rate, MN involvement and the extent of neurodegeneration. CSF p-NfH and NfL were significantly increased in ALS compared with healthy and disease controls, including patients with other forms of MND, and were higher in patients with more aggressive disease course, reflecting progression rate. We also evaluated neurofilament diagnostic accuracy in our centre, identifying with high sensitivity and 100% specificity cut-off values of 0.652 ng/mL for CSF p-NfH (P < .0001) and of 1261 pg/mL for NfL (P < .0001) in discriminating ALS from healthy controls. CSF neurofilaments were significantly correlated with ALS progression rate. Overall, CSF neurofilaments appear to reflect the burden of neurodegeneration in MND and represent reliable diagnostic and prognostic biomarkers in ALS.     

The Association Between Effective Dose of Magnesium and Mild Compulsive Exercise on Spatial Learning,Memory, and Motor Activity of Adult Male Rats

The relationship of minerals and trace elements with inflammatory bowel disease (IBD) is complex. Alterations in their metabolism can be induced by the diseases and their complications. To study the role of trace elements in IBD patients’ serum zinc and copper and their related enzymes, including superoxide dismutase (SOD), activity were measured in patients with IBD patients as well as in healthy subjects. In addition, the correlation between serum trace element levels, albumin, total protein, urea level, copper/zinc ratio, and disease activity (DA) was determined in these subjects. Serum samples were obtained from 35 patients (19 ulcerative colitis (UC) and 16 Crohn’s disease (CD)) in the active phase of the disease and 30 healthy control subjects. Serum levels of zinc, copper, SOD activity, albumin, total protein, and urea were measured. The results were compared between the two groups using independent Student’s t test in statistical analysis. Serum levels of zinc, SOD activity, albumin, and total protein were significantly lower (P < 0.05) in patients than controls, while serum urea level was significantly higher in patients compared to controls. Copper concentrations did not differ between patients with IBD (mean ± SD, 58.8 ± 20.7 μg/d) and controls (55.57 ± 12.6 μg/d). Decreased levels of zinc and SOD activity are associated with increased inflammatory processes indicating inappropriate antioxidant system in patients with IBD. Additionally, lower levels of albumin and total protein with higher level of urea reflect metabolic problems in liver system.     

Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients with leukemia

Essential elements, mainly selenium and zinc, were involved in protection against oxidative stress in cells. Oxidation could lead to the formation of free radicals that have been implicated in the pathogenesis of many diseases, including leukemia. Leukemia is a neoplastic disease that is susceptible to antioxidant enzyme and essential elements alterations. This study was undertaken to examine the levels of essential elements, antioxidant enzymes activities, and their relationships with different types of leukemia. Serum selenium, zinc, and copper concentrations, red blood cell glutathione peroxidase (GPx) activities, plasma Cu−Zn superoxide dismutase (Cu−Zn SOD) activities and lipid peroxidation (LPO) levels were determined in 49 patients with different types of leukemia before initial treatment. Serum selenium and zinc concentrations were lower in leukemia patients than those of controls (p<0.01). Serum copper concentration was higher in leukemia patients than that of controls (p<0.01). The activities GPx and Cu−Zn SOD were significantly increased in leukemia patients, especially with acute leukemia (AL), acute lymphoid leukemia (ALL), and acute nonlymphoid leukemia (ANLL) (p<0.05), whereas no difference was found between those of chronic myelogeneous leukemia and the controls. The levels of LPO were normal as controls. Serum selenium concentration was not correlated with GPx, and serum levels of zinc and copper were not related to Cu−Zn SOD. Serum zinc levels had a negative correlation with the absolute peripheral blast cells, whereas serum copper had a positive correlation with the absolute peripheral blast cells. Increased GPx and Cu−Zn SOD activities and normal levels of LPO, which were a protective responses, were an indicator of mild oxidative stress; it mights indicate that the essentials elements alterations in leukemia patients were mostly dependent on tumor activity. Changes of their levels demonstrated that there are low selenium, zinc, and high copper status in leukemia patients. The decrease of plasma zinc and increase of the Cu/Zn ratio could be the index that showed an unfavorable prognosis of acute leukemia.