Molecular and Chemical Neuropathology

, Volume 23, Issue 2–3, pp 115–124 | Cite as

Freed-amino acids in human cerebrospinal fluid of alzheimer disease, multiple sclerosis, and healthy control subjects

  • George H. Fisher
  • Leonard Petrucelli
  • Christina Gardner
  • Carolyn Emory
  • William H. Frey
  • Luigi Amaducci
  • Sandro Sorbi
  • Giovanna Sorrentino
  • Mauro Borghi
  • Antimo D'aniello
Article

Abstract

This is the first report of the presence of freeD-amino acids in lumbar and ventricular human cerebrospinal fluid (CSF) of individuals with Alzheimer disease (AD) compared with CSF of normal control subjects and with individuals affected by multiple sclerosis, as an unrelated neurologic disorder. Freed-amino acids are present at significantly higher levels in AD CSF than normal CSF, whereas in the CSF of patients affected by multiple sclerosis,d-amino acids occurs at the same level as in the normal controls. The totald-amino acid content in ventricular CSF was 1.48 times higher in the AD than controls (26.4 vs 17.9 nmol/mL,p=0.025). The totald-amino acid content was 1.43 times higher in AD lumbar CSF than controls (1.89 vs. 1.32 nmol/mL,p=0.001).d-Aspartate in particular was 2.74 times higher in AD ventricular CSF compared to normal ventricular CSF (3.34 vs 1.22 nmol/mL,p=0.029). In lumbar CSF,d-aspartate was 1.5 times higher in AD than controls (0.054 vs 0.036 nmol/mL,p=0.041). Previously we reported thatd-amino acids are elevated in AD brain proteins associated with neurofibrillary tangles compared to normal brain proteins (D'Aniello et al., 1992c; Fisher et al., 1992a,b). Thus, thed-amino acids present in CSF may originate from degradation of brain proteins.

Index Entries

d-Amino acids cerebrospinal fluid ventricular CSF lumbar CSF Alzheimer disease multiple sclerosis aspartic acid 

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References

  1. Aswad D. W. (1984) Determination ofd- andl-aspartate in amino, acid mixtures by high performance liquid chromatography after derivatization with a chiral adduct ofo-phthaldialdehyde.Anal. Biochem. 137, 405–407.PubMedCrossRefGoogle Scholar
  2. Barber J. R. and Clarke S. (1983) Membrane protein carboxyl methylation increases with human erythrocyte age.J. Biol. Chem. 258, 1189–1196.PubMedGoogle Scholar
  3. Coy D. H., Kastin A. J., Schally A. V., Morin O., Caron N. G., Labrie F., Walker J. M., Fertel R., Berntson G. G., and Sandman C. A. (1976) Synthesis and opiate activities of stereoisomers and otherd-amino acid analogs of methionine-enkephalin.Biochem. Biophys. Res. Commun. 73, 632–637.PubMedCrossRefGoogle Scholar
  4. D'Aniello A. and Giuditta A. (1977) Identification ofd-aspartic acid in the brain ofOctopus vulgaris L. J. Neurochem. 29, 1053–1057.PubMedCrossRefGoogle Scholar
  5. D'Aniello A. and Giuditta A. (1978) Presence ofd-aspartate in squid axoplasm and in other regions of the cephalopod nervous system.J. Neurochem. 31, 1107–1108.PubMedCrossRefGoogle Scholar
  6. D'Aniello A. and Giuditta A. (1980) Presence ofd-alanine in crustacean muscle and hepatopancreas.Comp. Biochem. Physiol. 66B, 319–322.Google Scholar
  7. D'Aniello A., D'Onofrio G., and Pischetola M. (1987) Determination ofd-aspartate content in lenses of human cataracts using a new method of hydrolysis to minimize racemization of amino acids.Ital. J. Biochem. 36, 322A-324A.Google Scholar
  8. D'Aniello A., Nardi G., Cipollaro M., Pischetola M., and Padula L. (1990) Occurrenced-alanine in the eggs and the developing embryo of the sea urchinParacentrotus lividus.Comp. Biochem. Physiol. 97B, 291–294.Google Scholar
  9. D'Aniello A., Nardi G., Vetere A., and Ferguson G. P. (1992a) Occurrence of freed-aspartic acid in the circumsoesophageal ganglia ofAplysia fasciata.Life Sci. 52, 733–736.CrossRefGoogle Scholar
  10. D'Aniello A., Vetere A., and Padula L. (1992b) Occurrence of freed-amino acids in the gametes, embryos, larvae and adult of the sea squirtCiona intestinalis.Comp. Biochem. Physiol. 102B, 795–797.Google Scholar
  11. D'Aniello A., Vetere A., Fisher G. H., Cusano G., Chavez M., and Petrucelli L. (1992c) Presence ofd-Alanine in proteins of normal and Alzheimer human brain.Brain Res. 592, 44–48.PubMedCrossRefGoogle Scholar
  12. D'Aniello A., Vetere A., and Petrucelli L. (1993) Further study on the specificity ofd-amino acid oxidase andd-aspartate oxidase and time course for complete oxidation ofd-amino acids.Comp. Biochem. Physiol. 105B, 731–734.Google Scholar
  13. D'Aniello A., Petrucelli L., Gardner C., and Fisher G. (1993) Improved method for hydrolyzing proteins and peptides without inducing racemization and for determining their trued-amino acid content.Anal. Biochem. 213, 290–295.PubMedCrossRefGoogle Scholar
  14. Dunlo D. S., Neidle A., McHale D., Dunlop D. M., and Lajtha A. (1986) The presence of freed-aspartic acid in rodents and man.Biochem. Biophys. Res. Commun. 142, 27–32.CrossRefGoogle Scholar
  15. Felbeck H. and Wiley S. (1987) Freed-amino acids in the tissue of marine bivalves.Biol. Bull. 173, 252–259.CrossRefGoogle Scholar
  16. Ferraro T. N. and Hare T. A. (1984) Triple-column ion-exchange physiological amino acid analysis with fluorescent detection; baseline characterization of human cerebrospinal fluid.Anal. Biochem. 143, 82–94.PubMedCrossRefGoogle Scholar
  17. Fisher G. H., D'Aniello A., Vetere A., Padula L., Cusano G. P. and Man E. H. (1991) Freed-aspartate andd-alanine in normal and Alzheimer brain.Brain Res. Bull. 26, 983–985.PubMedCrossRefGoogle Scholar
  18. Fisher G. H., Payan I. L., Chou S. J., Man E. H., Cerwinski S., Martin T., Emory C., and Frey W. H. (1992a) Racemizedd-aspartate in Alzheimer neurofibrillary tangles.Brain Res. Bull. 28, 127–131.PubMedCrossRefGoogle Scholar
  19. Fisher G. H., D'Aniello A., Vetere A., Cusano G., Chávez M. and Petrucelli L. (1992b) Quantification ofd-aspartic acid in normal and Alzheimer brains.Neurosci. Lett. 143, 215–218.PubMedCrossRefGoogle Scholar
  20. Godel H., Graser T., Földi P., Pfaender P., and Fürst P. (1984) Measurement of free amino acids in human biological fluids by high-performance liquid chromatography.J. Chromatogr. 297, 49–61.PubMedCrossRefGoogle Scholar
  21. Hashimoto A., Nishikawa T., Oka T. and Takahashi K. (1993a) Endogenousd-serine in rat brain:N-methyl-d-aspartate receptor-related distribution and aging.J. Neurochem. 60, 783–786.PubMedCrossRefGoogle Scholar
  22. Hashimoto A., Kumashiro S., Nishikawa T., Oka T., Takahashi K., Mito T., Takashima S., Doi N., Mizutani Y., Yamazaki T., Kaneko T. and Ootomo E. (1993b) Embryonic development and postnatal changes in freed-aspartate andd-serine in the human prefrontal cortex.J. Neurochem. 61, 348–351.PubMedCrossRefGoogle Scholar
  23. Helfman P. M. and Bada J. L. (1976) Aspartic acid racemization in dentine as a measure of aging.Nature 262, 279–281.PubMedCrossRefGoogle Scholar
  24. Kamatani Y., Minakata H., Kenny P. T. M., Iwashita T., Watanabe K., Funase K., Sun X. P., Yongisiri A., Kim K. H., Novales-Li P., Novales E. T., Lanapi C. G. Takeuchi H., and Nomoto K. (1989) Achatin-I, an endogenous neuroexcitatory tetrapeptide fromAchatina fulica ferussac containing ad-amino acid residue.Biochem. Biophys. Res. Commun. 160, 1015–1020.PubMedCrossRefGoogle Scholar
  25. Khachaturian Z. S. (1985) Diagnosis of Alzheimer's disease.Arch. Neurol. 42, 1097–1105.PubMedGoogle Scholar
  26. Man E. H., Sandhouse E. H., Burg J., and Fisher G. H. (1983) Accumulation ofd-aspartic acid with age in human brain.Science 222, 1407, 1408.CrossRefGoogle Scholar
  27. Man E. H., Fisher G. H., Payan I. L., Cadilla-Perezrios R., Garcia N. M., Chemburkar R., Arends G. and Frey W. H., II. (1987)d-Aspartate in human brain.J. Neurochem. 48, 510–515.PubMedCrossRefGoogle Scholar
  28. Masters P. M., Bada J. L., and Zigler J. S. (1977) Aspartic acid racemization in human lens during aging and in cataract formation.Nature 268, 71–73.PubMedCrossRefGoogle Scholar
  29. Mirra S. S., Heyman A., McKeel D., Sumi S. M., Crain B. J., Brownlee L. M., Vogel F. S., Hughes J. P., van Belle G., Berg L., and participating CERAD neuropathologists (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) II. Standardization of the neuropathologic assessment of Alzheimer's disease.Neurology 41, 479–486.PubMedGoogle Scholar
  30. Montecucchi P. C., De Castgiglione R., Piani S. and Erspamer V. (1981) Amino acid composition and sequence of dermorphin, a novel opiate-like peptide from skin ofPhyllomedusa sauvage.Int. J. Pept. Prot. Res. 17, 275–283.CrossRefGoogle Scholar
  31. Nagata Y., Akino T., Ohno K., Kataoka Y., Ueda T., Sakuri T., Shiroshita K., and Yasuda T. (1987) Freed-amino acids in human plasma in relation to senescence and renal diseases.Clin. Sci. 73, 330–332.Google Scholar
  32. Nagata Y., Akino T. and Ohno K. (1989) Presence of freed-amino acids in mouse tissues.Experientia 45, 330–32.PubMedCrossRefGoogle Scholar
  33. Nagata Y., Yamamoto K., Shimojo T., Konno R., Yasumura Y., and Akino T. (1992) The presence of freed-alanine,d-proline, andd-serine in mice.Biochim. Biophys. Acta 1115, 208–211.PubMedGoogle Scholar
  34. Neidle A. and Dunlop D. S. (1990) Developmental changes in freed-aspartic acid in the chicken embryo and in the neonatal rat.Life Sci. 46, 1517–1522.PubMedCrossRefGoogle Scholar
  35. Ohto N., Kuhota I., Takao T., Shimomishi Y., Kamatamo Y., Minaketa M., Nomota K., Muneko Y., and Kobuyashi M. (1989) Fulicine, a novel neuropeptide containing ad-amino acid residue isolated from the ganglia ofAchatine fulica.Biochem. Biophys. Res. Commun. 178, 486–493.CrossRefGoogle Scholar
  36. Perry T. L., Hansen S., and Kennedy J. (1975) CSF amino acid and plasma-CSF amino acid ratios in adults.J. Neurochem. 24, 587–589.PubMedCrossRefGoogle Scholar
  37. Pomara N., Singh R., Deptula D., Chou J. C.-Y., Schwartz M. B., and LeWitt P. A. (1992) Glutamate and other CSF amino acids in Alzheimer's disease.Am. J. Psych. 149, 251–254.Google Scholar
  38. Preston R. L. (1987) Occurrence ofd-amino acids in higher organisms: A survey of the distribution ofd-amino acids in marine invertebrates.Comp. Biochem. Physiol. 87B, 55–62.Google Scholar
  39. Sato M., Yamaguchi T., Kanno N., and Saro Y. (1989) Confirmation ofd-aspartic acid in the novel dipeptide β-aspartylglycine isolated from tissue extract ofAplysia furodai.Biochem. J. 263, 617–620.PubMedGoogle Scholar
  40. Spink D. C., Swann J. W., Snead O. C., Wainewski R. A., and Martin D. L. (1986) Analysis of aspartate and glutamate in human cerebrospinal fluid by high performance liquid chromatography with automated precolumn derivatization.Anal. Biochem. 158, 79–86.PubMedCrossRefGoogle Scholar
  41. Tomiyama T., Asano S., Furiya YH., Shirasawa T., Noriaki E., and Mori H. (1994) Racemization of Asp23 residue affects the aggregation properties of Alzheimer amyloid β protein analogues.J. Biol. Chem. 269, 10205–10208.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 1994

Authors and Affiliations

  • George H. Fisher
    • 1
  • Leonard Petrucelli
    • 1
  • Christina Gardner
    • 1
  • Carolyn Emory
    • 2
  • William H. Frey
    • 2
  • Luigi Amaducci
    • 3
  • Sandro Sorbi
    • 3
  • Giovanna Sorrentino
    • 3
  • Mauro Borghi
    • 4
  • Antimo D'aniello
    • 5
  1. 1.Department of ChemistryBarry UniversityMiami Shores
  2. 2.Alzheimer's Treatment and Research Center Ramsey ClinicSt. Paul-Ramsey Medical CenterSt. Paul
  3. 3.Departimento di Scienze Neurologiche e PsichiatricheUniversity of FlorenceFlorenceItaly
  4. 4.Department of Medical Jurisprudence Policlinico Le ScotteUniversity of SienaItaly
  5. 5.Department of Biochemistry and Molecular BiologyStazione Zoologica ‘A Dohrn’NaplesItaly

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