Advertisement

Neurochemical investigations in patients with dementia of Alzheimer type and their clinical value

  • L. Frölich
  • A. Dirr
  • M. E. Götz
  • Y. Taneli
  • J. Thome
  • K. P. Lesch
  • R. Ihl
  • T. Dierks
  • D. Blum-Degen
  • P. Riederer
  • K. Maurer
Conference paper
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

The clinical diagnosis of dementia of Alzheimer type (DAT) relies on the identification of a dementia syndrome in the absence of other known etiologies, which results in a diagnostic validity of approximately 90 percent. Thus, the identification of a biological ante-mortem marker of DAT would be of great help. Investigations on post-mortem tissue have established several cascades of cell biological events in the affected brain, e.g. cholinergic degeneration, free oxygen radical toxicity, impairment of glucose metabolism, which we used as a rationale for testing the diagnosis utility of related parameters in DAT patients. Acetylcholine (ACh) and choline, and vitamin E in the CSF as well as neuroendocrine changes after a GHRH/CRH challenge and hormonal changes after an oral glucose tolerance in DAT patients were measured. For ACh concentration in CSF and neuroendocrine changes after GHRH as well as insulin release after OGTT, there were subtle changes from controls. The potential use of these parameters as diagnostic markers of Alzheimer’s disease in the alive patient is discussed.

Keywords

Oral Glucose Tolerance Test Senile Dementia Medial Temporal Lobe Atrophy Choline Level BioI Psychiatry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams Jr JD, Klaidman LK, Odunze IN, Shen HC, Miller CA (1991) Alzheimer’s and Parkinson’s disease — brain levels of glutathione, glutathione disulfide, and Vitamin E. Mol Chem Neuropathol 14:213–226.PubMedCrossRefGoogle Scholar
  2. Adem A, Nordberg, A, Bucht, G, Winblad B (1986) Extraneuronal cholinergic markers in Alzheimer’s and Parkinson’s disease. Prog Neurosycho-pharmocol Biol Psychiatry 10:247–257.CrossRefGoogle Scholar
  3. Aharon-Peretz J, Harel T, Revach M, Ben-Haim SA (1992) Increased sympathetic and decreased parasympathetic cardiac innervation in patients with Alzheimer’s disease. Arch Neurol 49:919–922.PubMedCrossRefGoogle Scholar
  4. Alom J, Galard R, Catalan R, Castellanos JM, Schwartz S, Tolosa E (1990) Cerebrospinal fluid neuropeptide Y in Alzheimer’s disease. Eur Neurol 30:207–210.PubMedCrossRefGoogle Scholar
  5. Arendt T, Bigl V, Arendt A, Tennstedt A (1983) Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease. Acta Neuropathol 61:101–108.PubMedCrossRefGoogle Scholar
  6. Atack JR, Perry EK, Bonham JR, Perry RH, Tomlinson BE, Blessed G, Fairbairn A (1983) Molecular forms of acetylcholinesterase in senile dementia of ALzheimer type: selective loss of the intermediate (10S) form. Neurosci Lett 40:199–204.PubMedCrossRefGoogle Scholar
  7. Blass JP (1993a) Pathophysiology of the Alzheimer’s syndrome. Neurology 43[Suppl 4]:25–38.Google Scholar
  8. Blass JP (1993b) Metabolic alterations common to neural and non-neural cells in Alzheimer’s disease. Hippocampus 3:45–54.PubMedGoogle Scholar
  9. Blass JP, Sheu RK, Cedarbaum JM (1988) Energy metabolism in disorders of the nervous system. Rev Neurol (Paris) 144:543–563.Google Scholar
  10. Blessed G, Tomlinson BE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114:797–811.PubMedCrossRefGoogle Scholar
  11. Bucht G, Adolfsson R, Lithner F, Winblad B (1983) Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. Acta Med Scand 213:387–392.PubMedCrossRefGoogle Scholar
  12. Cutler NR (1988) Utility of biological markers in the evaluation and diagnosis of Alzheimer’s disease. Brain Dysfunct 1:12–31.Google Scholar
  13. DeKosky St T, Scheff St W, Hackney CG (1989) Acetylcholine synthesis in human CSF: implications for study of central cholinergic metabolism. Neurochem Res 14:191–196.PubMedCrossRefGoogle Scholar
  14. Elble R, Giacobini E, Higgins C (1989) Choline levels are increased in cerebrospinal fluid of Alzheimer patients. Neurobiol Aging 10:45–50.PubMedCrossRefGoogle Scholar
  15. Foley P, Bradford HF, Docherty M, Fillit H, Luine VN, McEwen B, Bucht G, Winblad B, Hardy J (1988) Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer’s disease. J Neurol 235:466–471.PubMedCrossRefGoogle Scholar
  16. Friedland RP (1993) Alzheimer’s disease: clinical features and differential diagnosis. Neurology 43[Suppl 4]:45–51.Google Scholar
  17. Friedland RP, Brun A, Budinger TF (1985) Pathological and positron emission tomographic correlations in Alzheimer’s disease. Lancet i:228.CrossRefGoogle Scholar
  18. Frölich L, Eilles C, Ihl R, Maurer K, Lanczik M (1989) Stage-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res 29:347–350.CrossRefGoogle Scholar
  19. Frölich L, Kornhuber J, Ihl R, Fritze J, Maurer K, Riederer P (1991) Integrity of the blood-CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG. Eur Arch Psychiatry Clin Neurosci 240:363–366.PubMedCrossRefGoogle Scholar
  20. Fujisawa Y, Sasaki K, Akiyama K (1991) Increased insulin levels after OGTT load in peripheral blood and cerebrospinal fluid of patients with dementia of Alzheimer type. Biol Psychiatry 30:1219–1228.PubMedCrossRefGoogle Scholar
  21. Götz ME, Freyberger A, Riederer P (1990) Oxidative stress: a role in the pathogenesis of Parkinson’s disease. J Neural Transm [Suppl 29]:241–249.Google Scholar
  22. Gsell W, Moll G, Sofic E, Riederer P (1993) Cholinergic and monoaminergic neurotransmitter system in patients with Alzheimer’s disease and senile dementia of the Alzheimer type: a critical evaluation. In: Maurer K (ed) Dementias, neurochemistry, neuropathology, neuroimaging, neurpsychology and genetics. Vieweg, Braunschweig, pp 25–51.Google Scholar
  23. Gsell W, Conrad R, Hickethier M, Sofic E, Frölich L, Wichart I, Jellinger K, Moll G, Ransmayr G, Beckmann H, Riederer P (1994) Decrease in catalase activity and inducibility of Superoxide dismutase activity in brains of patients with senile dementia of Alzheimer type. Neurochem (in press).Google Scholar
  24. Hachinski V, Iliff LD, Zilkha E, et al (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637.PubMedCrossRefGoogle Scholar
  25. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623.PubMedCrossRefGoogle Scholar
  26. Hollander E, Mohs RC, Davis KL (1986) Antemortem markers of Alzheimer’s disease. Neurobiol Aging 7: 367–387.PubMedCrossRefGoogle Scholar
  27. Hoyer S, Oesterreich K, Wagner O (1988) Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J Neurol 235:143–148.PubMedCrossRefGoogle Scholar
  28. Ihl R, Frölich L, Dierks T, Martin E, Maurer K (1992) Differential validity of psychometric tests in dementia of the Alzheimer type. Psychiatry Res 44:93–106.PubMedCrossRefGoogle Scholar
  29. Jobst KA, Smith AD, Szatmari M, Molyneux A, Esiri ME, King E, Jaskowski A, McDonald B, Wald N (1992) Detection in life of confirmed Alzheimer’s disease using a simple measurement of medial temporal lobe atrophy by computed tomography. Lancet 340:1179–1183.PubMedCrossRefGoogle Scholar
  30. Jobst KA, Smith AD, Barker CS, Wear A, King EM, Smith A, Anslow PA, Molyneux AJ, Shepstone BJ, Soper N, Holmes KA, Robinson JR, Hope RA, Oppenheimer C, Brockbank K, McDonald B (1992) Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 55:190–194.PubMedCrossRefGoogle Scholar
  31. Kaye JA, May C, Atack JR, Daly E, Sweeney DL, Beal MF, Kaufman S, Milstien S, Friedland RP, Rapoport SI (1988) Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer’s disease. Ann Neurol 24:647–650.PubMedCrossRefGoogle Scholar
  32. Kesslak JP, Nalcioglu O, Cotman CW (1991) Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer’s disease. Neurology 41:51–54.PubMedGoogle Scholar
  33. Kilander L, Boberg M, Lithell H (1992) Peripheral glucose metabolism and insulin sensitivity in Alzheimer’s disease (poster, unpublished).Google Scholar
  34. Kristensen E, Jakobsen J, Bartels U, Vestergaard P (1989) Cholinergic dysfunction of heart, pupil, salivary glands, and urinary bladder in healthy volunteers during long-term treatment with clomipramine. Psychopharmacology 98:398–402.PubMedCrossRefGoogle Scholar
  35. Kukull WA, Larson EB, Reifler BV, Lampe TH, Yerby MS, Hughes JP (1990) The validity of 3 clinical diagnostic criteria for Alzheimer’s disease. Neurology 40:1364–1369.PubMedGoogle Scholar
  36. Kumar V, Giacobini E, Markwell S (1989) CSF choline and acetylcholinesterase in early-onset vs. late-onset Alzheimer’s disease patients. Acta Neurol Scand 80:461–466.PubMedCrossRefGoogle Scholar
  37. Lesch KP, Rupprecht R (1990) Psychoneuroendocrine research in depression. II. Hormone responses to releasing hormones as a probe for hypothalamic-pituitary-endorgan dysfunction. J Neural Transm 75:179–194.CrossRefGoogle Scholar
  38. Lesch KP, Ihl R, Frölich L, Rupprecht R, Müller U, Schulte H-M, Maurer K (1990) Endocrine responses to growth hormone releasing hormone and corticotriopin releasing hormone in early-onset Alzheimer’s disease. Psychiatry Res 33:107–112.PubMedCrossRefGoogle Scholar
  39. Matsumoto M, Togashi H, Yoshioka M, Morii K, Hirokami M, Tochihara M, Ikeda T, Saito Y, Saito H (1991) Significant correlations between cerebrospinal fluid and brain levels of norepindephrine, serotonin and acetylcho-line in anesthetized rats. Life Sci 48:823–829.PubMedCrossRefGoogle Scholar
  40. Maurer K, Ihl R, Frölich L (1993) Alzheimer. Springer, Berlin Heidelberg New York Tokyo.CrossRefGoogle Scholar
  41. McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T (1984) Aging, Alzheimer’s disease and the cholinergic system of the basal forebrain. Neurology 34:741–745.PubMedGoogle Scholar
  42. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944.PubMedGoogle Scholar
  43. Metcalfe T, Bowen DM, Muller DPR (1989) Vitamine E concentrations in human brain of patients with Alzheimer’s disease, fetuses with Down’s syndrome, centenarians and controls. Neurochem Res 14:1209–1212.PubMedCrossRefGoogle Scholar
  44. Navaratnam DS, Priddle JD, McDonald B, Esiri MM, Robbinson JR, Smith AD (1991) Anomalous molecular form of acetylcholinesterase in cerebrospinal fluid in histologically diagnosed Alzheimer’s disease. Lancet 337:447–449.PubMedCrossRefGoogle Scholar
  45. Okuyama S, Ikeda Y (1988) Determination of acetylcholine and choline in human cerebrospinal fluid using high-performance liquid chromatography combined with an immobilized enzyme reactor: ageing-induced change of acetylcholine level. J Chromatogr 431:389–394.PubMedCrossRefGoogle Scholar
  46. Pearlson GD, Harris GJ, Power RE, Barta PE, Camargo E, Chase GA, Noga JT, Tune LE (1992) Quantitative changes in mesial temporal volume, regional cerebral blood flow and cognition in Alzheimer’s disease. Arch Gen Psychiatry 49:402–408.PubMedCrossRefGoogle Scholar
  47. Pomara N, Singh R, Deptula D, LeWitt PA, Bissette G, Stanley M, Nemeroff CB (1989) CSF Corticotrophin-Releasing Factor (CRF) in Alzheimer’s disease: its relationship to seventy of dementia and monoamine metabolites. Biol Psychiatry 26:500–504.PubMedCrossRefGoogle Scholar
  48. Raskind MA, Peskind ER, Veith RC, Risse St C, Lampe TH, Borson S, Gumbrecht G, Dorsa DM (1989) Neuroendocrine responses to physostigmine in Alzheimer’s disease. Arch Gen Psychiatry 46:535–540.PubMedCrossRefGoogle Scholar
  49. Reed BR, Jagust WJ, Seab Ph, Ober BA (1989) Memory and regional cerebral blood flow in mildly symptomatic Alzheimer’s disease. Neurology 39:1537–1539.PubMedGoogle Scholar
  50. Schapiro MB, Atack JR, Hanin I, Max C, Haxby JV, Rapoport St I (1990) Lumbar cerebrospinal fluid choline in healthy aging and in Down’s syndrome. Arch Neurol 47:977–980.PubMedCrossRefGoogle Scholar
  51. Shen ZX, Ding Q, Wei CZ, Ding MC, Meng JM (1993) CSF Cholinesterase in early-onset and late-onset Alzheimer’s disease and multi-infarct dementia of Chinese patients. Acta Neurol Scand 87:19–24.PubMedCrossRefGoogle Scholar
  52. Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D (1989) Mitochondrial function in brain tissue in primary degenerative dementias. Brain Res 436:30–38.CrossRefGoogle Scholar
  53. Stadler H, Nesslhut T (1986) Simple and rapid measurement of acetylcholine and choline by HPLC and electrochemical detection. Neurochem Int 9:127–129.PubMedCrossRefGoogle Scholar
  54. Teelken AW, Schuring HF, Trieling WB, Damsma G (1991) Measurement of acetylcholine and choline in cerebrospinal fluid by means of HPLC (poster, unpublished).Google Scholar
  55. Vatassery GT, Smith WE (1987) Detection of alpha-tocopherol quinone (vitamin E quinone) in human serum, platelets and red cell membrane samples. Anal Biochem 167:411–417.PubMedCrossRefGoogle Scholar
  56. Vatasseiy GT, Nelson MJ, Maletta GJ, Kuskowski MA (1991) Vitamin E (tocopherols) in human cerebrospinal fluid. Am J Clin Nutr 53:95–99.Google Scholar
  57. Wallace DC (1992) Mitochondrial genetics: a paradigm for aging and degenerative disease? Science 256:628–632.PubMedCrossRefGoogle Scholar
  58. Winograd C-H, Jacobson D, Minkoff J-R, Peabody C-A, Taylor B-S, Widirow L, Yesavage J-A (1991) Blood glucose and insulin response in patients with senile dementia of the Alzheimer’s type. Biol Psychiatry 30:507–511.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1994

Authors and Affiliations

  • L. Frölich
    • 1
  • A. Dirr
    • 2
  • M. E. Götz
    • 2
  • Y. Taneli
    • 2
  • J. Thome
    • 1
  • K. P. Lesch
    • 2
  • R. Ihl
    • 3
  • T. Dierks
    • 1
  • D. Blum-Degen
    • 2
  • P. Riederer
    • 2
  • K. Maurer
    • 1
  1. 1.Department of Psychiatry IJ. W. Goethe University of Frankfurt/MainFrankfurt/MainFederal Republic of Germany
  2. 2.Department of PsychiatryUniversity of WürzburgGermany
  3. 3.Department of PsychiatryUniversity of DüsseldorfFederal Republic of Germany

Personalised recommendations