Tyrosine hydroxylase, tryptophan hydroxylase, biopterin and neopterin in the brains and biopterin and neopterin in sera from patients with Alzheimer’s disease

  • T. Nagatsu
  • M. Sawada
  • M. Hagihara
  • N. Iwata
  • H. Arai
  • R. Iizuka
Part of the Key Topics in Brain Research book series (KEYTOPICS)


The activities of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and the concentrations of biopterin (BP) and neopterin (NP) were examined in postmortem brains from histologically verified patients of senile dementia of Alzheimer type (SDAT). The results suggest that the reductions in TH, TPH, and BP may be related to the reduction in monoamine neurotransmitters, due to destruction of monoaminergic neurons in SDAT, and may be an event independent of the cholinergic dysfunction. Serum BP levels were also significantly reduced in patients with SDAT.


Tyrosine Hydroxylase Locus Coeruleus Senile Dementia Tryptophan Hydroxylase Cholinergic Dysfunction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adolfsson R, Gottfries CG, Roose BE, Winblad B (1979) Changes in brain catecholamines in patients with dementia of Alzheimer-type. Br J Psychiatry 135: 216–223PubMedCrossRefGoogle Scholar
  2. Arai H, Kobayashi K, Ikeda K, Nagao Y, Ogihara R, Kosaka K (1983) A computed tomography study of Alzheimer’s disease. J Neurol 229: 60–77CrossRefGoogle Scholar
  3. Arai H, Kosaka K, Iizuka R (1984) Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia. J Neurochem 43: 388–393PubMedCrossRefGoogle Scholar
  4. Bondareff W, Mountjoy CQ, Roth M (1981) Selective loss of neurons of adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Lancet 1: 783–784PubMedCrossRefGoogle Scholar
  5. Bowen DM, Smith CB, White P, Davison AN (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and the abiotrophies. Brain 99: 457–496Google Scholar
  6. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254PubMedCrossRefGoogle Scholar
  7. Brenneman AR, Kaufman S (1964) The role of tetrahydropteridines in the enzymatic conversion of tyrosine to 3,4-dihydroxyphenylalanine. Biochem Biophys Res Commun 17: 177–183CrossRefGoogle Scholar
  8. Candy JM, Perry RH, Perry EK, Irving D, Blessed G, Fairbairn AF, Tomlinson BE (1983) Pathological changes in the nucleus of Meynert in Alzheimer’s and Parkinson’s disease. J Neurol Sci 59: 227–289CrossRefGoogle Scholar
  9. Cross AJ, Crow TJ, Perry RH, Blessed G, Tomlinson BE (1981) Reduced dopamine beta-hydroxylase activity in Alzheimer’s disease. Br Med J 282: 93–94CrossRefGoogle Scholar
  10. Cross AJ, Crow TJ, Johnson JA, Joseph MH, Perry EK, Perry RH, Blessed G, Tomlinson BE (1983) Monoamine metabolism in senile dementia of Alzheimer type. J Neurol Sci 60: 383–392PubMedCrossRefGoogle Scholar
  11. Davies P, Maloney AJ (1976) Selective loss of control cholinergic neurons in Alzheimer’s disease. Lancet 11: 1430Google Scholar
  12. Forno LS (1978) The locus coeruleus in Alzheimer’s disease. J Neuropathol Exp Neurol 37: 614CrossRefGoogle Scholar
  13. Friedman PA, Kappelman AH, Kaufman S (1972) Partial purification and characterization of tryptophan hydroxylase from rabbit bind brain. J Biol Chem 247: 4165–4173PubMedGoogle Scholar
  14. Henke H, Lang W (1983) Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of Alzheimer-type patients. Brain Res 267: 281–291PubMedCrossRefGoogle Scholar
  15. Hirano A, Zimmerman HM (1962) Alzheimer’s neurofibrillary changes: a topographic study. Arch Neurol 7: 227–242PubMedCrossRefGoogle Scholar
  16. Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi 0 (1970) Enzymatic studies on the biosynthesis of serotonin in mammalian brain. J Biol Chem 245: 1699–1709Google Scholar
  17. Ishii T (1966) Distribution of Alzheimer’s neurofibrillary changes in the brain stem and hypothalamus of senile dementia. Acta Neuropathol 6: 181–187PubMedCrossRefGoogle Scholar
  18. Lovenbeg W, Jequire E, Sjoerdsma A (1967) Tryptophan hydroxylase: measurement in pineal gland, brain stem and carcinoid tumors. Science 155: 217–219CrossRefGoogle Scholar
  19. Mann DMA, Yates PO (1983) Serotonin nerve cells in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 46: 96–98PubMedCrossRefGoogle Scholar
  20. Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J Biol Chem 239: 2910–2917Google Scholar
  21. Nagatsu T, Oka K, Kato T (1979) Highly sensitive assay for tyrosine hydroxylase activity by high-performance liquid chromatography. J Chromatogr 163: 247–252PubMedCrossRefGoogle Scholar
  22. Nagatsu T, Yamaguchi T, Kato T, Sugimoto T, Matsuura S, Akino M, Tsushima S, Nakazawa N, Ogawa H (1981) Radioimmunoassay for biopterin in body fluids and tissues. Anal Biochem 110: 182–189PubMedCrossRefGoogle Scholar
  23. Nagatsu T, Sawada M, Yamaguchi T, Sugimaoto T, Matsuura S, Akino M, Nakazawa N, Ogawa H (1984) Radioimmunoassay for neopterin in body fluids and tissues. Anal Biochem 141: 472–480PubMedCrossRefGoogle Scholar
  24. Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE (1977) Neurotransmitter enzyme abnormalities in senile dementia. J Neurol Sci 34: 247–265PubMedCrossRefGoogle Scholar
  25. Rossor MN, Svendsen C, Hunt SP, Mountjoy CQ, Roth M, Iversen LL (1982 a) The substantia innominata in Alzheimer’s disease: a histochemical and biochemical study of cholinergic marker enzymes. Neurosci Lett 28: 217–222Google Scholar
  26. Rossor MN, Garrett NJ, Johnson AL, Mountjoy CQ, Roth M, Iversen LL (1982 b) A post mortem study of the cholinergic and GABA systems in senile dementia. Brain 105: 313–330Google Scholar
  27. Sawada M, Nagatsu T, Nagatsu I, Ito K, lizuka R, Kondo T, Narabayashi H (1985) Tryptophan hydroxylase activity in the brains of controls and parkinsonian patients. J Neural Transm 62: 107–115PubMedCrossRefGoogle Scholar
  28. Sawada M, Hirata Y, Arai H, Iizuka R, Nagatsu T (1987) Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brains of normal controls and patients with senile dementia of Alzheimer type. J Neurochem 48: 760–764PubMedCrossRefGoogle Scholar
  29. Whitehouse PJ, Price DL, Clark AW, Coyle TT, DeLong M (1981) Alzheimer disease: evidence for a selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10: 122–126PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1990

Authors and Affiliations

  • T. Nagatsu
    • 1
  • M. Sawada
    • 2
  • M. Hagihara
    • 1
  • N. Iwata
    • 1
  • H. Arai
    • 3
  • R. Iizuka
    • 3
  1. 1.Department of BiochemistryNagoya University School of MedicineNagoyaJapan
  2. 2.Institute of Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan
  3. 3.Department of Psychiatry, School of MedicineJuntendo UniversityTokyoJapan

Personalised recommendations