Electroanalytical characterization of Alzheimer's disease and ovine spongiform encephalopathy by repeated cyclic voltammetry at a capillary graphite paste electrode

Abstract

Linear sweep voltammetry (sweep rate, 1–10 mV/s) of biological fluids impregnating electrodes made of electrochemically inert compressed graphite powder allows all electrochemically oxidizable compounds which are present in these fluids to be characterized rapidly and cheaply, without preliminary separation, by peaks occurring at specific potentials, and their concentrations to be quantified by the corresponding peak areas or heights. The main components normally present in biological fluids which can be characterized at specific potentials by this electroanalytical technique are ascorbate, urate, xanthin, oxalate, tyrosine, tryptophan, 5-HIAA, VMA, HVA, and some other minor catabolites of catecholamines and serotonin. The oxidation peaks of these components frequently correspond to irreversible oxidations, sometimes generating reversibly oxidizable products which are detected on the first return sweep and in further backward and forward sweeps by a reduction peak which usually occurs at a lower potential than the primary oxidation. The voltammetric profiles obtained for urine samples are remarkably constant when these samples come from healthy patients, but they may undergo substantial quantitative or qualitative alterations with specific features when various types of drugs are administered or pathologies are present. Characteristic features are observed in the urine of patients e.g. after administration of paracetamol, benzodiazepins, opiates and folinic acid. The perfusion of cisplatinum or carboplatinum derivatives results in the formation of a peak which has been attributed to 2, 8-dihydroxyadenine. Strong reductions in the amplitudes of most peaks relating to catabolites which are normally present are observed in urine samples from newborn children. Very strong and sensitive increases in the amplitudes of several peaks appear in urine samples from patients with a variety of inflammatory reactions. Qualitative variations resulting in the formation of peaks which are not normally detected in urine are observed in patients suffering from Alzheimer's disease. An epidemiological survey of the correlation between the amplitude of the reduction at 850 mV (vs. the standard hydrogen electrode) on the first return sweep and the clinical indexes in use for the identification of senile dementia have shown that the presence of these electrochemical characteristics is specific for degenerative dementia. Urine samples from sheep affected by spongiform encephalopathy, identified by post-mortem histology of brain tissues, have demonstrated the presence of the same electrochemical characteristics. The catabolite responsible for the electrochemical features described above, which has not yet been structurally identified, is not extracted by the organic solvents used for performing chromatographic analysis of catecholamines or indolic catabolites. In conclusion, in view of the relatively low cost of the equipment and execution, this method could be systematically used for rapid and cheap control of the effects of many drugs and for prediagnosis screening of several pathological conditions.