Higher S100B Concentrations Research Articles

S100B polymorphisms are associated with age of onset of Parkinson\u2019s disease

BackgroundIn this study we investigated the association between SNPs in the S100B gene and Parkinson’s disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD.MethodsThe SNPs rs9722, rs2239574, rs881827, rs9984765, and rs1051169 of the S100B gene were genotyped using the KASPar® PCR SNP genotyping system in a case-control study of two populations (431 PD patients and 465 controls, 195 PD patients and 378 controls, respectively). The association between the genotype and allelic distributions and PD risk was evaluated using Chi-Square and Cox proportional hazards test, as well as logistic regression. Linear regression and Cox proportional hazards tests were applied to assess the effect of the rs9722 genotypes on age of disease onset.ResultsThe S100B SNPs tested were not associated with the risk of PD. However, in both cohorts, the T allele of rs9722 was significantly more common in early onset PD patients compared to late onset PD patients. The SNP rs9722 was significantly related to age of onset, and each T allele lowered disease onset with 4.9 years. In addition, allelic variants of rs881827, rs9984765, and rs1051169, were significantly more common in early-onset PD compared to late-onset PD in the pooled population.Conclusionsrs9722, a functional SNP in the 3’-UTR of the S100B gene, was strongly associated with age of onset of PD.

S100b as a prognostic biomarker in outcome prediction for patients with severe traumatic brain injury.

As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) (n = 138 subjects) and serum (n = 80 subjects) samples across a 6-day time course. Long-bone fracture, Injury Severity Score (ISS), and isolated head injury status were variables used to assess extracerebral sources of S100b in serum. After TBI, CSF and serum S100b levels were increased over healthy controls across the first 6 days post-TBI (p ≤ 0.005 and p ≤ 0.031). Though CSF and serum levels were highly correlated during early time points post-TBI, this association diminished over time. Bivariate analysis showed that subjects who had temporal CSF profiles with higher S100b concentrations had higher acute mortality (p < 0.001) and worse Glasgow Outcome Scale (GOS; p = 0.002) and Disability Rating Scale (DRS) scores (p = 0.039) 6 months post-injury. Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores (p = 0.032), temporal serum profiles were associated with acute mortality (p = 0.015). High CSF S100b levels were observed in women (p = 0.022) and older subjects (p = 0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.

S100B and schizophrenia

The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium-binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated.

The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease

BackgroundCognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood.MethodsThirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies. Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject.ResultsThe hippocampal volume was significantly smaller in COPD patients compared to the control group. It is positively correlated with a mini mental state examination (MMSE) score, SaO2 in mild-to-moderate COPD patients, the levels of PaO2 in both mild-to-moderate and severe COPD patients. Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects. S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients.ConclusionsHippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD. Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD.

The Influence of Experimental Alcohol Load and Alcohol Intoxication on S100B Concentrations

Because nearly 50% of patients with mild head trauma are alcohol intoxicated, it often remains unclear if the neurological deficits are due to alcohol intoxication or to intracerebral damage. To avoid unnecessary head computed tomography investigations in patients with mild head trauma, S100B is currently used as an exclusion marker for cellular brain damage. However, whether S100B levels are influenced by alcohol itself remains to be unclear. Therefore, we performed a case-control study of nontraumatized, alcohol-intoxicated patients to prove if serum S100B is altered by alcohol uptake. Furthermore, we investigated if alcohol infusions combined with an initial oral alcohol load up to a blood alcohol steady state of 100 mg/dL affected S100B levels in healthy volunteers (n = 12). In this standardized experimental procedure, no significant increase in S100B levels could be found. In contrast, compared with the control group (n = 60 sober and healthy), the ethyl alcohol-intoxicated patients (n = 61; mean ethyl alcohol, 251 [SD, 87] mg/dL) had higher S100B concentrations (0.193 [SD, 0.45] vs. 0.063 [SD, 0.059] μg/L; P < 0.001), and 39% of them had levels greater than the pathologic cutoff at greater than 0.104 μg/L. However, no significant correlation was found between ethyl alcohol concentrations and S100B within the respective group. Our clinical data suggest that blood alcohol concentrations far in excess of 100 mg/dL are associated with increased S100B levels in alcohol-intoxicated patients.

Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males

Severe traumatic brain injury (TBI) is associated with a 30%-70% mortality rate. S100B has been proposed as a biomarker for indicating outcome after TBI. Nevertheless, controversy has arisen concerning the predictive value of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to determine whether S100B serum levels correlate with primary outcome following isolated severe TBI or multitrauma in males. Twenty-three consecutive male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS) 3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting of eight healthy volunteers were enrolled in this prospective study. Clinical outcome variables of severe TBI comprised: survival, time to intensive care unit (ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU discharge]. Venous blood samples were taken at admission in the ICU (study entry), 24 h later, and 7 days later. Serum S100B concentration was measured by an immunoluminometric assay. At study entry (mean time 10.9 h after injury), mean S100B concentrations were significantly increased in the patient with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations when compared with survivors (0.85 microg/L). In fact, there was a significant correlation between higher initial S100B concentrations and fatal outcome (Spearman's =0.485, p=0.019). However, there was no correlation between higher S100B concentrations and the presence of multitrauma. The specificity of S100B in predicting mortality according to the cut-off of 0.79 microg/L was 73% at study entry. Increased serum S100B levels constitute a valid predictor of unfavourable outcome in severe TBI, regardless of the presence of associated multitrauma.