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Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease

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Molecular and Chemical Neuropathology

Abstract

Quantitative analysis of total gangliosides and of ganglioside composition by HPTLC has been carried out on the gray matter of frontal cerebral cortex of six brains from Down’s syndrome (DS) adults, six age-matched controls, six Alzheimer’s disease (AD) adults, and six controls matched for age with the AD brains, as well as on three DS and six control cerebellum specimens. In addition, the analyses were carried out on specimens of corpus callosum of five adult DS and five control brains. No abnormalities were found in the gangliosides of DS corpus callosum. In DS frontal cortex, the concentration of total gangliosides was reduced, and there was a decrease in the fraction of GT1b and GD1b′ and an increase in those of GT1a′ GD3′ GM1 and GM2; the ratio of total b-series to a-series gangliosides was decreased. Very similar abnormalities were found in the gangliosides of DS cerebellum. In AD frontal cortex, by contrast, the total gangliosides and their composition were normal by comparison with agematched controls, with the minor exception of reductions in the fractions of GQ1b and GT1L. It is concluded that abnormalities in gangliosides exist in the brain in DS that are unrelated to AD-type pathology and may reflect developmental disturbances.

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Abbreviations

DS:

Down’s syndrome

NANA:

N-Acetylneuraminic acid

ChAT:

Choline acetyltransferase

AD:

Alzheimer’s disease

HPTLC:

High-performance thinlayer chromatography

References

  • Ando S., Chang N.-C., and Yu R. K. (1978) High-performance thin-layer chromatography and densitometric determination of brain ganglioside composition of several species.Anal. Biochem. 89, 437–450.

    Article  PubMed  CAS  Google Scholar 

  • Ando S. (1983) Gangliosides in the nervous system.Neurochem. Int. 5, 507–537.

    Article  CAS  Google Scholar 

  • Baker R. E. (1988) Gangliosides as cell-adhesion factors in the formation of selective connections within the nervous system.Prov. Brain Res. 73, 491–508.

    Article  CAS  Google Scholar 

  • Bowen D. M., Smith C. B., White P., Flack R. H. A., Carrasco L. H., Gedye J. L., and Davison A. N. (1987) Chemical pathology of the organic dementias. II. Quantitative estimation of cellular changes in post-mortem brains.Brain,100, 427–453.

    Article  Google Scholar 

  • Brooksbank B. W. L. and Balázs R. (1988) Development and aging of the brain in a common human aneuploidy—Down’s syndrome,Handbook of Human Growth and Developmental Biology (Meisami E. and Timiras P. S., eds.), vol. I, part C, pp. 21–44, CMC, Boca Raton, FL.

    Google Scholar 

  • Brooksbank B. W. L., and Martinez, M. (1989) Lipid abnormalities in the brain in adult Down’s syndrome and Alzheimer’s disease.Molec. Chem. Neuropathol.,11, ...

    Google Scholar 

  • Brooksbank B. W. L., Walker D., Balázs R., and Jørgensen O. S. (1989) Neuronal maturation in the foetal brain in Down’s syndrome.Early Hum. Dev. 18, 237–246.

    Article  PubMed  CAS  Google Scholar 

  • Candy J. M., Perry E. K., Perry R. M., Court J. A., Oakley A. E., and Edwardson J. A. (1986) The current status of the cortical cholinergic system in Alzheimer’s disease and Parkinson’s disease.Prog. Brain Res. 65, 105–132.

    Article  Google Scholar 

  • Chan K. F. (1987) Ganglioside-modulated protein phosphorylation. Partial purification and characterization of a ganglioside-stimulated protein kinase in brain.J. Biol. Chem. 262, 5248–5255.

    PubMed  CAS  Google Scholar 

  • Cherayil G. D. (1969) Estimation of glycolipids in four selected lobes of human brain in neurological diseases.J. Neurochem. 16, 913–920.

    Article  PubMed  CAS  Google Scholar 

  • Collerton D. (1986) Cholinergic function and intellectual decline in Alzheimer’s disease.Neuroscience 19, 1–28.

    Article  PubMed  CAS  Google Scholar 

  • Coyle J. T., Oster-Granite M. L., and Gearhart J. D. (1986) The neurobiologic consequences of Down’s syndrome.Brain Res. Bull. 16, 773–787.

    Article  PubMed  CAS  Google Scholar 

  • Crino P. B., Ullman M. D., Vogt B. A., Bird E. D., and Volicer L. (1989) Brain gangliosides in dementia of the Alzheimer type.Arch. Neurol. 46, 398–401.

    PubMed  CAS  Google Scholar 

  • DeKosky S. T. and Bass N. H. (1982) Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex.Neurology 32, 1227–1233.

    PubMed  CAS  Google Scholar 

  • Fonnum F. (1975) A rapid radiochemical method for the determination of choline acetyltransferase.J. Neurochem. 24, 407–409.

    Article  PubMed  CAS  Google Scholar 

  • Ghidoni R., Sonnino S., Tettamanti G., Baumann N., Reuter G., and Schauer, R. (1980) Isolation and characterization of a trisialoganglioside from mouse brain, containing 9-O-acetyl-N-acetylneuraminic acid.J. Biol. Chem. 255, 6990–6995.

    PubMed  CAS  Google Scholar 

  • Gorio A. (1986) Ganglioside enhancement of neuronal differentiation, plasticity and repair.CRC Crit. Rev. Clin. Neurobiol. 2, 241–296.

    PubMed  CAS  Google Scholar 

  • Hakomori S.-I. (1981) Glycospingolipids in cellular interaction, differentiation and oncogenesis.Annu. Rev. Biochem. 50, 733–764.

    Article  PubMed  CAS  Google Scholar 

  • Hardy, J., Adolfsson R., Alafuzoff I., Bucht G., Marcusson J., Nyberg P., Perdahl E., Wester P., and Winblad B. (1985) Transmitter deficits in Alzheimer’s disease.Neurochem. Int. 4, 545–573.

    Article  Google Scholar 

  • Harth S., Dreyfus H., Urban P. F., and Mandel P. (1978) Direct thin-layer chromatography of gangliosides of a total lipid extract.Anal. Biochem. 86, 543–551.

    Article  PubMed  CAS  Google Scholar 

  • Kraĉun I., Rösner H., Cosovič C., and Stavljenič A. (1984) Topographical atlas of the gangliosides of the adult human brain.J. Neurochem. 43, 979–989.

    Article  PubMed  Google Scholar 

  • Kundu S. K. (1981) Thin-layer chromatography of neutral glycosphingolipids and gangliosides.Methods Enzymol. 72, 185–204.

    Article  PubMed  CAS  Google Scholar 

  • Ledeen R. W. (1983) Gangliosides,Handbook of Neurochemistry, Metabolism in the Nervous System 2nd ed., vol. 3 (Lajtha A., ed.), pp. 41–90, Plenum, New York.

    Google Scholar 

  • Ledeen R. W. (1984) Biology of gangliosides: Neuritogenic and neuronotrophic properties.J. Neurosci. Res. 12, 147–159.

    Article  PubMed  CAS  Google Scholar 

  • Ledeen R. W. and Yu R. K. (1982) Ganglioside structure, isolation and analysis.Methods Enzymol. 83, 139–191.

    Article  PubMed  CAS  Google Scholar 

  • Leon A., Facci L., Toffano G., Sonnino S., and Tettamanti G. (1981) Activation of (Na+, K+)-ATPase by nanomolar concentrations of GM1 ganglioside.J. Neurochem. 37, 350–357.

    Article  PubMed  CAS  Google Scholar 

  • McCoy E. E. and Sneddon J. M. (1983) Cell biological aspects of Down’s syndrome.Adv. Cell. Neurobiol. 4, 249–261.

    CAS  Google Scholar 

  • Majocha R. E., Jungalwala F. B., Rodenrys A., and Marotta C. A. (1989) Monoclonal antibody to embryonic CNS antigen A2B5 provides evidence for the involvement of membrane components at sites of Alzheimer degeneration and detects sulfatides as well as gangliosides.J. Neurochem. 53, 953–961.

    Article  PubMed  CAS  Google Scholar 

  • Mann D. M. A. (1988) The pathological association between Down syndrome and Alzheimer disease.Mech. Ageing Dev. 43, 99–136.

    Article  PubMed  CAS  Google Scholar 

  • Miettinen T. and Takki-Luukainen I. T. (1959) Use of butyl acetate in determination of sialic acid.Acta Chem. Scand. 13, 856–858.

    Article  CAS  Google Scholar 

  • Oliver C. and Holland A. J. (1986) Down’s syndrome and Alzheimer’s disease: A review.Psychol. Med. 16, 307–322.

    Article  PubMed  CAS  Google Scholar 

  • Rösner H. (1982) Ganglioside changes in the chicken optic lobes as biochemical indicators of brain development and maturation.Brain Res. 236, 49–61.

    Article  PubMed  Google Scholar 

  • Scott B. S., Becker L. E., and Petit T. L. (1983) Neurobiology of Down’s syndrome.Prog. Neurobiol. 21, 199–237.

    Article  PubMed  CAS  Google Scholar 

  • Segler-Stahl K., Webster J. C., and Brunngraber E. G. (1983) Changes in the concentration and composition of human brain gangliosides with aging.Gerontology 29, 161–168.

    Article  PubMed  CAS  Google Scholar 

  • Sinex F. M. and Merrill C. R. (eds.) (1982) Alzheimer’s disease, Down’s syndrome and aging.Ann. NY Acad. Sci. 396.

  • Sorbi S., Piacentini S., and Amaducci L. (1987) Intralaminar distribution of neurotransmitter-related enzymes in cerebral cortex of Alzheimer’s disease.Gerontology 33, 197–202.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K. (1965) The pattern of mammalian brain gangliosides. II. Evaluation of the extraction procedures, post-mortem changes and the effect of formalin preservation.J. Neurochem. 12, 629–638.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K., Katzman R., and Korey S. (1965) Chemical studies on Alzheimer’s disease.J. Neuropathol. Exp. Neurol. 24, 211–224.

    Article  PubMed  CAS  Google Scholar 

  • Svennerholm L. (1957) Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method.Biochim. Biophys. Acta 24, 604–611.

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson, B. E. (1980) The structural and quantitative aspects of the dementias,Biochemistry of Dementia (Roberts P. J., ed.), pp. 25–52, Wiley, New York.

    Google Scholar 

  • Ueno K., Ando S., and Yu R. K. (1978) Gangliosides of human, cat, and rabbit spinal cords and cord myelin.J. Lipid Res. 19, 863–871.

    PubMed  CAS  Google Scholar 

  • Urban P. F., Harth S., Freysz L., and Dreyfus H. (1980) Brain and retinal ganglioside composition from different species determined by TLC and HPTLC,Structure and Function of Gangliosides (Svennerholm L., Mandel P., Dreyfus H., and Urban P. F., eds.), pp. 149–157, Plenum, New York.

    Google Scholar 

  • Vanier M. T., Holm M., Ohman R., and Svennerholm L. (1971) Developmental profiles of gangliosides in human and rat brain.J. Neurochem. 18, 581–592.

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski K. E., Wisniewski H. M., and Wen G. Y. (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome.Ann. Neurol. 17, 278–282.

    Article  PubMed  CAS  Google Scholar 

  • Yates A. J. (1986) Gangliosides in the nervous system during development and regeneration.Neurochem. Pathol. 5, 309–329.

    Article  PubMed  CAS  Google Scholar 

  • Yavin E. and Yavin Z. (1979) Ganglioside profiles during neural tissue development, acquisition in the prenatal rat brain and cerebral cell cultures.Dev. Neurosci. 2, 25–37.

    Article  CAS  Google Scholar 

  • Zanetta J. P., Vitiello F., and Vincendon G. (1980) Gangliosides from rat cerebellum: Demonstration of considerable heterogeneity using a new solvent for thin layer chromatography.Lipids 15, 1055–1061.

    Article  CAS  Google Scholar 

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Brooksbank, B.W.L., McGovern, J. Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease. Molecular and Chemical Neuropathology 11, 143–156 (1989). https://doi.org/10.1007/BF03160048

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  • DOI: https://doi.org/10.1007/BF03160048

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