Skip to main content
Log in

Alzheimer’s and Parkinson’s disease

Brain levels of glutathione, glutathione disulfide, and vitamin E

  • Published:
Molecular and Chemical Neuropathology

Abstract

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two, groups of patients with neurodegeneration: those with Alzheimer’s disease (AD), and AD with some features of Parkinson’s disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8, μg/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 μg/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 μg/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adams J. D., Lauterburg B. H., and Mitchell J. R. (1983) Plasma glutathione and glutathione disulfide in the rat: Regulation and response to oxidative stress.J. Pharmacol. Exp. Ther. 227, 749–754.

    PubMed  CAS  Google Scholar 

  • Adams J. D., Klaidman L. K., and Odunze I. N. (1989) Oxidative effects of MPTP in the midbrain.Res. Commun. Subst. Abuse 10, 169–180.

    CAS  Google Scholar 

  • Bergeron C. and Pollanen M. (1989) Lewy bodies in Alzheimer disease —one or two diseases?Alzheimer Dis. Assoc. Disorders 3, 197–204.

    CAS  Google Scholar 

  • Boller F., Mizutani T., Roessmann U., and Gambetti, P. (1980) Parkinson disease, dementia and Alzheimer disease: Clinicopathological correlations.Ann. Neurol. 7, 329–335.

    Article  PubMed  CAS  Google Scholar 

  • Brown M. S. and Goldstein J. L. (1986) A receptor-mediated pathway for cholesterol homeostasis.Science 232, 34–47.

    Article  PubMed  CAS  Google Scholar 

  • Chui H. C., Mortimer J. A., Slager U., Zarow C., Bondareff W., and Webster D. D. (1986) Pathologic correlates of dementia in Parkinson’s disease.Arch. Neurol. 43, 991–995.

    PubMed  CAS  Google Scholar 

  • Clement M., and Bourre J. M. (1990) Alteration of α-tocopherol content in the developing and aging peripheral nervous system: Persistence of high correlations with total and specific (n-6) polyunsaturated fatty acids.J. Neurochem. 54, 2110–2117.

    Article  PubMed  CAS  Google Scholar 

  • Dexter D. T., Carter C. J., Wells F. R., Javoy-Agid F., Agid Y., Lees A., Jenner P., and Marsden C. D. (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease.J. Neurochem. 52, 381–389.

    Article  PubMed  CAS  Google Scholar 

  • Dexter D. T., Wells F. R., Agid F., Agid Y., Lees A. J., Jenner P., and Marsden C. D. (1987) Increased nigral iron content in postmortem parkinsonian brain.Lancet 2, 1219–1220.

    Article  PubMed  CAS  Google Scholar 

  • Ditter S. M. and Mirra S. S. (1987) Neuropathologic and clinical features of Parkinson’s disease in Alzheimer’s disease patients.Neurology 37, 754–760.

    PubMed  CAS  Google Scholar 

  • Factor S. A., Sanchez-Ramos J. R., and Weiner W. J. (1990) Vitamin E therapy in Parkinson’s disease.Adv. Neurol. 53, 457–461.

    PubMed  CAS  Google Scholar 

  • Fariss M. W., Pascoe G. A., and Reed D. J. (1985) Vitamin E reversal of the effect of extracellular calcium on chemically induced toxicity in hepatocytes.Science 227, 751–754.

    Article  PubMed  CAS  Google Scholar 

  • Gallo-Torres H. E. (1985) Transport and metabolism, inFat Soluble Vitamins: Their Biochemistry and Applications (Diplock A., ed.), pp. 193–267, Technomic, Lancaster, Great Britain.

    Google Scholar 

  • Goss-Sampson M. A., MacEvilly C. J., and Muller D. P. R. (1988) Longitudinal studies of the neurobiology of vitamin E and other antioxidant systems, and neurological function in the vitamin E deficient rat.J. Neurol. Sci. 87, 25–35

    Article  PubMed  CAS  Google Scholar 

  • Goss-Sampson M. A. and Muller D. P. R. (1987) Studies on the neurobiology of vitamin E and some other antioxidant systems in the rat.Neuropath. Appl. Neurobiol. 13, 289–296.

    Article  CAS  Google Scholar 

  • Growdon J. H. and Corkin S. (1986) Cognitive impairments in Parkinson’s disease.Adv. Neurol. 45, 383–392.

    Google Scholar 

  • Hoyer S. (1986) Senile dementia and Alzheimer’s disease, brain blood flow and metabolism.Prog. Neuro-Psychopharmacol. Biol. Psychiat. 10, 447–478.

    Article  CAS  Google Scholar 

  • Hunter S. (1985) The rostral mesencephalon in Parkinson’s disease and Alzheimer’s disease.Acta Neuropathol. 68, 53–58.

    Article  PubMed  CAS  Google Scholar 

  • Jackson C. V. E., Holland A. J., Williams C. A., and Dickerson J. W. T. (1988) Vitamin E and Alzheimer’s disease in subjects with Down’s syndrome.J. Mental Defic. Res. 32, 479–484.

    Google Scholar 

  • Khachaturian Z. S. (1985) Diagnosis of Alzheimer’s disease.Arch. Neurol. 42, 1097–1105.

    PubMed  CAS  Google Scholar 

  • Kish S. J., Morito C., and Hornykiewicz, O. (1985) Glutathione peroxidase activity in Parkinson’s disease brain.Neurosci. Lett. 58, 343–346.

    Article  PubMed  CAS  Google Scholar 

  • Kosaka K. (1978) Lewy bodies in cerebral cortex, report of three cases.Acta Neuropath. 42, 127–134.

    Article  PubMed  CAS  Google Scholar 

  • Kosaka K., Oyanagi S., Matsushita M., Hori A., and Iwase S. (1976) Presenile dementia with Alzheimer-, Pick- and Lewy-body changes.Acta Neuropath. 36, 221–233.

    Article  PubMed  CAS  Google Scholar 

  • Martins R. N., Harper C. G., Stokes G. B., and Masters C. L. (1986) Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer’s disease may reflect oxidative stress.J. Neurochem. 46, 1042–1045.

    Article  PubMed  CAS  Google Scholar 

  • McCay P. B., Brueggemann G., Lai E. K., and Powell S. R. (1989) Evindence that α-tocopherol functions cyclically to quench free radicals in hepatic microsomes.Ann. New York Acad. Sci. 570, 32–45.

    Article  CAS  Google Scholar 

  • McKhann G., Drachman D., Folstein M., Katzman R., Price D., and Stadlan E. M. (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services task force of Alzheimer’s disease.Neurology 34, 939–944.

    PubMed  CAS  Google Scholar 

  • Metcalfe T., Bowen D. M., and Muller D. P. R. (1989) Vitamin E concentrations in human brai of patients with Alzheimer’s disease, fetuses with Down’s syndrome, centenarians, and controls.Neurochem. Res. 14, 1209–1212.

    Article  PubMed  CAS  Google Scholar 

  • Murphy D. J. and Mavis R. D. (1981a) A comparison of the in vitro binding of α-tocopherol to microsomes of lung, liver, heart and brain of the rat.Biochim. Biophys. Acta 663, 390–400.

    PubMed  CAS  Google Scholar 

  • Murphy D. J. and Mavis R. D. (1981b) Membrane transfer of α-tocopherol.J. Biol Chem. 256, 10464–10468.

    PubMed  CAS  Google Scholar 

  • Nakashima S. and Ikuta F. (1985) Catecholamine neurons with Alzheimer’s neurofibrillary changes and alteration of tyrosine hydroxylase.Acta Neuropathol. 66, 37–41.

    Article  PubMed  CAS  Google Scholar 

  • Odunze I. N., Klaidman L. K., and Adams, J. D. (1990a) MPTP toxicity: Differential effects in the striatum, cerebral cortex and midbrain on glutathione, glutathione disulfide and protein sulfhydryl levels.Res. Commun. Subst. Abuse. 11, 123–134.

    CAS  Google Scholar 

  • Odunze I. N., Klaidman L. K., and Adams J. D. (1990b) MPTP toxicity in the mouse brain and vitamin E.Neurosci. Lett. 108, 346–349.

    Article  PubMed  CAS  Google Scholar 

  • Perry T. L., Godin D. V., and Hansen S. (1982) Parkinson’s disease: A disorder due to nigral, glutathione deficiency.Neurosci. Lett. 33, 305–310.

    Article  PubMed  CAS  Google Scholar 

  • Perry T. L. and Yong V. W. (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients.Neurosci. Lett. 67, 269–274.

    Article  PubMed  CAS  Google Scholar 

  • Perumal A. S., Tordzro W. K., Katz M., Jackson-Lewis V., Cooper T. B., Fahn S., and Cadet J. L. (1989) Regional effects of 6-hydroxydopamine on free radical scavengers in rat brain.Brain Res. 504, 139–141

    Article  PubMed  CAS  Google Scholar 

  • Phebus L. A., Perry K. W., Clemens J. A., and Fuller R. W. (1986) Brain anoxia releases striatal dopamine in rats.Life Sci. 38, 2447–2453.

    Article  PubMed  CAS  Google Scholar 

  • Riederer P., Sofic E., Rausch W. D., Schmidt B., Reynolds G. P., Jellinger K., and Youdim M. B. H. (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.J. Neurochem. 52, 515–520.

    Article  PubMed  CAS  Google Scholar 

  • Sims N. R., Bowen D. M., Neary D., and Davison A. N. (1983) Metabolic processes in Alzheimer’s Disease: Adenine nucleotide, content and production of14CO2 from [U-14C]glucose in vitro in human neocortex.J. Neurochem. 41, 1329–1334.

    Article  PubMed  CAS  Google Scholar 

  • Sims N. R., Finegan J. M., Blass J. P., Bowen D. M., and Neary D. (1987) Mitochondrial function in brain tissue in primary degenerative dementia.Brain Res. 436, 30–38.

    Article  PubMed  CAS  Google Scholar 

  • Slivka A., Mytilineou C., and Cohen G. (1987a) Histochemical evaluation of glutathione in brain.Brain Res. 409, 275–284.

    Article  PubMed  CAS  Google Scholar 

  • Slivka A., Spina M. B., and Cohen G. (1987b) Reduced and oxidized glutathione in human and monkey brain.Neurosci. Lett. 74, 112–118.

    Article  PubMed  CAS  Google Scholar 

  • Soderberg M., Edlund C., Kristensson K., and Dallner G. (1990) Lipid compositions of different regions of the human brain during aging.J. Neurochem. 54, 415–423.

    Article  PubMed  CAS  Google Scholar 

  • Traber M. G., Olivecrona T., and Kayden H. J. (1985) Bovine milk lipoprotein lipase transfers tocopherol to human fibroblasts during triglyceride hydrolysis in vitro.J. Clin. Invest. 75, 1729–1734.

    Article  PubMed  CAS  Google Scholar 

  • Vatassery G. T., Angerhofer C. K., and Knox, C. A. (1984a) Effect of age on vitamin E concentrations in various regions of the brain and a few selected peripheral tissues of the rat, and on the uptake of radioactive vitamin E by various regions of rat brain.J. Neurochem. 43, 409–412.

    Article  PubMed  CAS  Google Scholar 

  • Vatassery G. T., Angerhofer C. K., Knox C. A., and Desmukh D. S. (1984b) Concentrations of vitamin E in various neuroanatomical regions and subcellular fractions, and the uptake of vitamin E by specific areas, of rat brain.Biochim. Biophys. Acta 792, 118–122.

    PubMed  CAS  Google Scholar 

  • Vatassery G. T. and Hagen D. F. (1977) A liquid chromatographic method for quantitative determination of α-tocopherol in rat brain.Anal. Biochem. 79, 129–134.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adams, J.D., Klaidman, L.K., Odunze, I.N. et al. Alzheimer’s and Parkinson’s disease. Molecular and Chemical Neuropathology 14, 213–226 (1991). https://doi.org/10.1007/BF03159937

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03159937

Index Entries

Navigation