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  • Author or Editor: W. Markesbery x
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Abstract  

The time course and defining factors involved in the formation of neurofibrillarytangles (NFT) and senile plaques (SP) in Alzheimer's disease (AD) brainare unknown. Above ground nuclear weapons tests led to significantly increasedlevels of 14C in the carbon cycle. Because SP and NFT are relativelyresistant to degradation, the 14C levels in SP and NFT should reflecttheir year of formation. Through the use of accelerator mass spectrometry(AMS) and the measurement of 14C levels, we have determined theaverage age of formation of isolated SP and NFT fractions of 6 AD subjects.While a heterogeneous process of formation is indicated, NFT pre-date SP inthe majority of cases. In addition, it is clear that NFT and SP have a muchslower carbon turnover rate than normal brain tissue.

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Abstract  

Concentrations of 17 elements in fingernails of 92 control individuals with ages ranging from 4 months to 93 years living in a relatively non-industrial environment were determined by instrumental neutron activation analysis (INAA). Statistical analysis demonstrated several different patterns of trace element correlation with age and sex. Bromine, Co, Cr, Fe, Na and Sb were found to be negatively correlated (p<0.05) with age, while Zn was positively correlated (p<0.05). Silver, Au, Se, and Zn concentrations were found to be higher in females than in males. Males had higher concentrations of Na and K than females. Significant interelement correlations were also observed. The age and sex variations observed should prove to be useful in the proper interpretation of elemental imbalances associated with degenerative neurological diseases, especially in view of recent reports that markers for AD have been detected in external tissue.

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Abstract  

Chronic lead (Pb) intoxication has been linked to Alzheimer's disease (AD). Lead, like many heavy elements, tends to accumulate in bone. PIXE is a powerful analytical tool which permits the determination of Pb at the g/g level without requiring sample digestion. GFAAS is one of the most sensitive methods for the determination of Pb and is capable of determining ng/g levels in solution. For bone analyses by GFAAS, sample dissolution and a matrix modifier are required. Rib bone samples were analyzed for Pb by PIXE and GFAAS. IAEA Animal Bone (H-5) was used as a secondary standard for Pb with both methods to ensure accuracy. The range of Pb concentrations in human rib bone was 1.4–11.5 g/g for the trabecular surface by PIXE, 1.3–45 g/g for the cortical surface by PIXE, and 1.54–11.75 g/g for whole bone by GFAAS. No significant difference (p>0.05) was found for AD versus control for either surface or for whole bone.

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Abstract  

Laser microprobe mass spectrometry (LMMS) detection limits for mercury have been determined using mercury-doped Spurr's tissue embedding medium. Actual mercury concentrations were confirmed via INAA. Procedures have also been developed to measure lithium and indium concentrations in thin films of polymerized Spurr's samples via PIGE and PIXE. These elements are currently being investigated as laser power density internal standards in the analysis of human tissue for studies of trace element involvement in neurological diseases.

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Abstract  

The possible association of dental amalgam surface exposure, brain mercury (Hg) levels, and pathological markers of Alzheimer's disease (AD) in the brain is the subject of an on-going study in our laboratory. Two radiochemical neutron activation analysis methods and the use of instrumental neutron activation analysis (INAA) with Compton suppression spectrometry have been evaluated for improving our INAA Hg detection limit (2.8±0.6 ng/g, wet-weight basis) in human tissue. Large numbers of samples dictated the use of a purely instrumental method or rapid, simple radiochemical separations. Human brain tissues and NIST biological standards were analyzed using a precipitation of Hg2Cl2, a solvent extraction utilizing sodium diethyldithiocarbomate, conventional INAA, and INAA with Compton suppression. The radiochemical precipitation of Hg2Cl2 proved to be the most useful method for use in our study because it provided a simultaneous, quantitative determination of silver (Ag) and a Hg detection limit in brain tissue of 1.6±0.1 ng/g (wet-weight basis).

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Abstract  

Results of micro-PIXE analysis of senile plaques (SP) in Alzheimer's disease (AD) brain have been utilized to independently confirm levels of iron (Fe) as measured by LMMS in adjacent brain sections. LMMS concentrations were calculated based on the preparation and analysis of an iron calibration curve prepared in our laboratory. The LMMS standards consist of ironcis-dicyclohexano-18-crown-6 ether coordination complexes dissolved in Spurr's low viscosity embedding medium. To our knowledge, this is the first report of the use of micro-PIXE, with its spatial resolution and detection limits comparable to that of LMMS, in the validation of LMMS results. The agreement observed between results obtained for Fe by micro-PIXE and LMMS indicates that the use of our LMMS standards, at least in the case of Fe, yields accurate results.

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Abstract  

Reactor thermal neutron irradiation of biological matrices induces high levels of intense gamma-ray or bremsstrahlung radiation from82Br,42K,24Na, and32P, that interfere with the determination of As, Cd, Cu, and Mo by INAA. Central nervous system (CNS) issue samples from subjects with Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and controls were analyzed using a simple RNAA procedure involving a rapid two-step solvent extraction procedure to determine these four elements. Significant increases (p0.05) in concentrations of Cd and Mo were observed for brain of AD subjects compared to controls, but significant imbalances were not observed for ALS subjects. Concentration data for these elements in selected international reference standards are also presented.

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