Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease.

BACKGROUND: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. OBJECTIVE: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. METHODS: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-ß (Aß) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. RESULTS: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aß42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers. CONCLUSION: CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

Limited penetration of cobalt and chromium ions into the cerebrospinal fluid following metal on metal arthroplasty: a cross-sectional analysis.

Background: The purpose of this study was to determine the concentration of cobalt (Co) and chromium (Cr) ions in synovial fluid, blood plasma and cerebrospinal fluid (CSF) of patients with metal-on-metal (MoM) implants, and to assess the relationship between implant history and patient characteristics with ion concentrations in CSF.Methods: An observational, non-randomised cross-sectional study was conducted with patients presenting to a single surgeon for treatment of degenerative conditions of the hip and knee. Blood and fluid samples were collected intraoperatively and analysed for proteins and trace elements.Results: Overall, the presence of an implant was associated with significantly higher Co and Cr concentrations in plasma (controls 5-115 nmol/L Co, 5-232 nmol/L Cr; well-functioning implant recipients 5-469 nmol/L Co, 5-608 nmol/L Cr; hip revisions 6-546 nmol/L Co, 5-573 nmol/L Cr), and for Cr concentrations in CSF (controls 5-24 nmol/L; well-functioning implant recipients 6-36 nmol/L, hip revisions 7-32 nmol/L). In absolute terms, <1% of the levels observed in the joint fluid and <15% of plasma metals appeared in the CSF. Multivariable regression models suggested different transfer mechanisms of Co and Cr to the CSF, with the presence of an implant not associated with ion levels.Conclusion: The presence of MoM implants is associated with significantly higher plasma levels of Co and Cr but not CSF levels, and the CSF/plasma ratio appears to be influenced by the plasma concentration in a nonlinear fashion. Co and Cr may be transferred to the CSF by different mechanisms, and their concentrations appears dependent on other factors yet to be identified. Although higher levels of plasma ions are associated with above average CSF metal concentrations, the thresholds for neurotoxicity remain unclear and require further study.

Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid.

Abnormal interaction of beta-amyloid 42 (Abeta42) with copper, zinc and iron induce peptide aggregation and oxidation in Alzheimer's disease (AD). However, in health, Abeta degradation is mediated by extracellular metalloproteinases, neprilysin, insulin degrading enzyme (IDE) and matrix metalloproteinases. We investigated the relationship between levels of Abeta and biological metals in CSF. We assayed CSF copper, zinc, other metals and Abeta42 in ventricular autopsy samples of Japanese American men (N=131) from the population-based Honolulu Asia Aging Study. There was a significant inverse correlation of CSF Abeta42 with copper, zinc, iron, manganese and chromium. The association was particularly strong in the subgroup with high levels of both zinc and copper. Selenium and aluminum levels were not associated to CSF Abeta42. In vitro, the degradation of synthetic Abeta substrate added to CSF was markedly accelerated by low levels (2microM) of exogenous zinc and copper. While excessive interaction with copper and zinc may induce neocortical Abeta precipitation in AD, soluble Abeta degradation is normally promoted by physiological copper and zinc concentrations.

Determination of chromium in cerebrospinal fluid using electrothermal atomisation atomic absorption spectrometry.

A rapid method to determine the chromium content of cerebrospinal fluid (CSF) samples using electrothermal atomization atomic absorption spectrometry (ETA-AAS) with deuterium-arc background correction is described. The chromium concentration in CSF was evaluated by the standard addition method. Sample dilution (1 + 1) with 0.25% (m/v) Triton X-100 and 4.5% (v/v) HNO3 gave the best combination of sensitivity, reproducibility, and low blank reading compared with dilution using other solvents. Within-batch reproducibility was 3.2% for 20 CSF samples, between-batch reproducibility was 4.7%. CSF samples from 43 healthy volunteers collected in a manner designed to avoid contamination yielded chromium concentrations of 14.6 +/- 6.3 ng mL(-1).

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.

Concentrations of chromium, cesium, and tin in cerebrospinal fluid of patients with brain neoplasms, leukemia or other noncerebral malignancies, and neurological diseases.

We measured the concentrations of chromium, cesium, and tin in the cerebrospinal fluid (CSF) of 29 patients with brain tumors [21 benign (BBT) and eight malignant (MBT)], 28 leukemic patients, 14 patients with lymphoma or noncerebral solid tumors (NLCT), and 32 control patients (15 with neurological disorders and 17 with noneurological conditions) by use of flameless atomic absorption spectrophotometry. We detected chromium in 94% of the patients, tin in 79%, and cesium in 50%. The mean (and SEM) concentrations (micrograms/L) of these metals in the control group were 4.7 (1.1) for chromium, 3.8 (1.6) for cesium, and 6.4 (1) for tin. We observed significant differences (P less than 0.05) in the concentration of chromium in CSF between the MBT group and all other tumor groups; the ratios for the mean CSF concentration of chromium in patients with BBT, leukemia, or NLCT to that in patients with MBT were 2.6, 2.1, or 4.4, respectively. We saw no significant differences in the concentrations of cesium or tin among the various groups investigated.