W. D. Ehmann

Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease

We determined levels of thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, and the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), and catalase (CAT) in the amygdala, hippocampus, pyriform cortex, superior and middle temporal gyri, inferior parietal lobule, middle frontal gyrus, occipital pole, and cerebellum of 13 Alzheimers disease (AD) and 10 control brains. Levels of TBARS were elevated in all AD brain regions except the middle frontal gyrus, and elevation levels reached statistical significance in the hippocampus and pyriform cortex and marginal significance in the amygdala of AD subjects compared with age-matched controls. Significant elevation of GSH-Px activity was present in AD hippocampus compared with control. Moderate but statistically insignificant elevations of GSH-Px activity also were present in the amygdala and pyriform cortex in AD. GSSG-R activity was significantly elevated in the amygdala and hippocampus in AD subjects compared with controls. CAT activity was significantly elevated in AD hippocampus and superior and middle temporal gyri. SOD levels were elevated in all brain regions in AD patients compared with controls, although none of these elevations reached statistical significance. Antioxidant enzyme activities were significantly elevated where lipid peroxidation was most pronounced, suggesting a compensatory rise in antioxidant activity in response to increased free radical formation. This study supports the concept that the brain in AD is under increased oxidative stress and demonstrates that the oxidative changes are most pronounced in the medial temporal lobe, where histopathologic alterations are most severe. NEUROLOGY 1995;45: 1594-1601

Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress

Copper (Cu), iron (Fe), and zinc (Zn) levels in five different brain regions (amygdala, hippocampus, inferior parietal lobule, superior and middle temporal gyri, and cerebellum) were determined by instrumental neutron activation analysis (INAA) in samples from Alzheimers disease (AD) patients and age-matched control subjects. A significant decrease in Cu, and significant increases in Zn and Fe were found in AD hippocampus and amygdala, areas showing severe histopathologic alterations in AD. None of these elements were significantly imbalanced in the cerebellum which is minimally affected in AD.

Elevated 4-Hydroxynonenal in Ventricular Fluid in Alzheimer’s Disease

4-Hydroxynonenal (4-HNE), an aldehyde by-product of the peroxidation of fatty acids, has been shown to have toxic properties for neurons in culture. In light of increasing evidence that oxidative stress contributes to the neurodegenerative process in Alzheimers disease (AD), we quantified levels of free and protein-bound 4-HNE in the ventricular fluid from 19 AD subjects and 13 control subjects by high-pressure liquid chromatography and dot-blot immunoassay. Free 4-HNE levels were found to be significantly elevated in the ventricular fluid of AD subjects compared with control subjects (p = 0.0096). These results demonstrate increased lipid peroxidation in AD brain and suggest a role for 4-HNE in the neurodegenerative process.

Brain trace element concentrations in aging

Trace element concentrations were determined in various human brain regions over the complete life span using instrumental neutron activation analysis. Several different patterns of trace element alteration were observed with age. Brain Al, Cl and Na concentrations increase with advancing age, while K, P and Rb decline. Ag, Co, Fe, Sb and Sc concentrations increase up to the 40 to 79 age range then decline. Br, Se and Zn remain relatively constant throughout adult life. Hg, Mn and Cs show no consistent trend with age. In infant brains Br and Cl increase and Al, Cr, Cs, Fe, Mn, P, Rb, Sc, Se and Zn decrease compared to adults. The essential elements that remain within narrow concentration limits throughout adult life suggest the presence of an efficient homeostatic mechanism for their regulation in the brain, while those that are altered with age suggest modifications in control mechanisms or altered relationships with other elements. Increased concentrations of non-essential elements may reflect accumulation from our environment, impaired removal or altered balance with other elements.

Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study

We measured aluminum (Al), calcium (Ca), and iron (Fe) levels in neuronal cytoplasm and nucleus, capillaries, and neuropil in samples of ventral cervical spinal cord from 5 patients with sporadic amyotrophic lateral sclerosis (ALS) and 5 age-matched controls using laser microprobe mass spectrometry (LMMS). The concentration of Al was not altered in any area in the ALS samples. In contrast, Fe and Ca were increased 1.5-2-fold in the nucleus and cytoplasm of ALS neurons but not in capillaries and neuropil. These findings do not support the hypothesis that Al is enriched in spinal cord of sporadic ALS as has been reported for Guamanian ALS/Parkinsons dementia. The elevations of Fe in spinal neurons are consistent with reports of increased Fe in bulk samples of ALS spinal cord. The presence of increased Fe within spinal neurons may be significant in the pathogenesis of motor neuron degeneration by catalyzing the generation of reactive oxygen species within specific cells.

Elemental imbalances in the olfactory pathway in Alzheimer's disease

Concentrations of 11 trace elements were determined in 56 control and 98 Alzheimers disease (AD) olfactory bulb, olfactory tract, olfactory trigone, piriform cortex and amygdala specimens by instrumental neutron activation analysis. Iron and zinc were significantly elevated and bromine was significantly depleted in olfactory regions of AD patients, compared with normal age-matched control subjects. Elevated iron could possibly play a role in neuronal degeneration in AD by enhancing reactive free radical formation.

Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease.

Oxygen free radical damage is strongly implicated in the pathogenesis of familial motor neuron disease (MND) associated with mutation of the Cu/Zn superoxide dismutase gene, and may be relevant in sporadic MND. Selenium (Se) and iron (Fe) have important roles in free radical metabolism. Using neutron activation analysis we have demonstrated significant elevation of Se and Fe in lumbar spinal cord in MND cases (38) compared to controls (22). Analysis of enzymes involved in free radical scavenging showed a significant and specific increase in the activity of the selenoprotein enzyme glutathione peroxidase in MND spinal cord.

Gold and iridium in meteorites and some selected rocks

Abstract Gold and iridium abundances in stony meteorites and various meteoritic and terrestrial materials have been determined by the technique of neutron activation. Gold abundances in chondrites reported here and by Baedecker and Ehmann (1965) are in generally good agreement with published data of other workers. Compilation of all available gold data yields the following group averages (in units of 10 −9 g/g) : C1-140, C2-177,C3-184, Enstatite-322, H-group-228, L-group-162, LL-group-167. Iridium data were obtained by use of an improved radiochemical separation technique and also a non-destructive technique employing gamma-gamma coincidence spectrometry. Evidence is presented that some earlier iridium determinations via radiochemical separations may be subject to significant analytical error. Iridium concentrations for the various chondrite groups as determined by the non-destructive coincidence technique of this work are (in units of 10 −9 g/g): Cl-490, C2-608, C3-645, Enstatite-618, H-group-781, L-group-453, LL-group-371. The significance of the meteorite data to the life history of these objects is discussed, with particular reference to the metal-silicate fractionation process during the formation of the chondrites.

The distribution of some noble metals in meteorites and natural materials

Abstract Abundances of gold, iridium and platinum have been determined in a wide range of meteoritic and terrestrial materials. The technique of thermal neutron activation analysis, as used in this study, couples the advantages of high sensitivity and freedom from reagent and laboratory contamination. Abundances of these elements in the chondrites are used to derive values for their “cosmic” atomic abundances. Implications of the data to theories of nucleosynthesis and the chemical history of meteorites and tektites are discussed.

The abundance of mercury in meteorites and rocks by neutron activation analysis

Abstract Mercury abundances have been determined in all classes of chondritic meteorites, the principle classes of achondritic meteorites, alkali and tholeiitic basalts, differentiated tholeiitic basalt intrusions, possible lower crustal and upper mantle rock inclusions, and a collection of six standard crustal rocks. The analytical method used was based on thermal neutron activation. Relatively high mercury abundances in the carbonaceous chondrites, previously reported by Reed, Kigoshi and Turkevich, have been confirmed. Abundance data among the various classes of chondrites and achondrites suggest a more complex behavior for mercury in the evolution of the meteorites than had been previously proposed. Possible lower crustal or upper mantle materials exhibit high mercury abundances in the range of the basic achondrites while six standard crustal rocks have abundances in the range of only 0·004–0·04 ppm. Implications of the data with respect to the estimation of cosmic abundances, and the evolution of the meteorites and the earth are discussed.