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Phospholipide und Pathophysiologie bei der Alzheimer-Krankheit

  • Conference paper
Demenz

  • 122 Accesses

Zusammenfassung

Die Herabsetzung der Aktivität der Cholinacetyltransferase [des die Synthese von Acetylcholin (ACh) katalysierenden Enzyms] wurde als erstes der zahlreichen Neurotransmitteranomalien, die in den Gehirnen von Alzheimer-Patienten nachweisbar sind, beschrieben [4] und ist nach wie vor das am besten belegte Phänomen. Der ACh-Mangel ist eng mit dem Untergang von cholinergen Zellen verbunden [20] und geht zugleich mit dem Auftreten der für die Alzheimer-Krankheit charakteristischen senilen Plaques einher [26]. Er trägt vermutlich zu den bei diesem Krankheitsbild auffallenden Gedächtnisstörungen bei. Gehirne von Patienten mit Down-Syndrom weisen ähnliche pathologische Merkmale auf wie Alzheimer-Patienten im 4. Lebensjahrzehnt (neuere Übersicht in [6]). Bei ihnen besteht ebenfalls ein ACh-Mangel wie er bei der Alzheimer-Krankheit zu beobachten ist [16, 38]. Wir stellten die These auf, daß die Anfälligkeit cholinerger Neuronen für Schädigungen bei der Alzheimer-Krankheit möglicherweise auf ihrem einzigartigen doppelten Bedarf an Cholin beruht. Alle Zellen benötigen Cholin für den Einbau in Phosphatidylcholin (PCh), einen strukturellen Bestandteil biologischer Membranen, cholinerge Neuronen benötigen Cholin jedoch darüber hinaus auch für die Synthese von ACh [2].

Die Studie wurde unterstützt durch das National Institute of Aging P50AG05134, RO1AG08906 und das National Institute of Mental Health MH-28783

Übersetzung: Birgit Lamerz-Beckschäfer

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Literatur

  1. Barany M, Chang YC, Arus C, Rustan T, Frey WH (1985) Increased glycerol-3-phos-pharylcholine in post-mortem Alzheimer’s brain. Lancet I:517

    Article  Google Scholar 

  2. Blusztajn JK, Liscovitch M, Richardson UI (1987) Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. Proc Natl Acad Sci USA 84:5474–5477

    Article  PubMed  CAS  Google Scholar 

  3. Blusztajn JK, Wurtman RJ (1983) Choline and cholinergic neurons. Science 221:614–620

    Article  PubMed  CAS  Google Scholar 

  4. Bowen DM, Smith CB, White P, Davison AN (1976) Neurotransmitter related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99:459–496

    Article  PubMed  CAS  Google Scholar 

  5. Cohen BM, Zubenko GS, Babb SM (1987) Abnormal platelet membrane composition in Alzheimer’s-type dementia. Life Sci 40:2445–2451

    Article  PubMed  CAS  Google Scholar 

  6. Coyle JT, Oster-Granite ML, Reeves RH, Gearhart JD (1988) Down syndrome. Alzheimer’s disease and the trisomy 16 mouse. TINS 11:390–394

    PubMed  CAS  Google Scholar 

  7. Cunico R, Anton G, Mayer C, Wehr T, Sheehan TL (1986) High sensitivity amino acid analysis using a novel automated precolumn derivatization system. Bio Chromatogr 1:6–14

    CAS  Google Scholar 

  8. Dujindan-van den Berge MR, Goekoop JG (1986) Lymphocyte concanavalin A capping: A similarity between Down’s syndrome and early onset primary degenerative dementia. J Neurol Neurosurg Psychiatry 49:595–598

    Article  Google Scholar 

  9. Ebstein RP, Oppenheim G, Zlotogorski Z, van Dijk Y, Doron A, Stessmann J (1986) Age-post-receptor changes in cyclic AMP second messenger signal amplification in normal aging and dementia of the Alzheimer type. Life Sci 39:1167–1175

    Article  PubMed  CAS  Google Scholar 

  10. Farooqui AA, Liss L, Horrocks LA (1988) Neurochemical aspects of Alzheimer’s disease: Involvement of membrane phospholipids. Metab Brain Dis 3:19–35

    Article  PubMed  CAS  Google Scholar 

  11. Goldberg AM, McCaman RE (1973) The determination of picomole amounts of acetylcholine in mammalian brain. J Neurochem 20:1–8

    Article  PubMed  CAS  Google Scholar 

  12. Hicks N, Brammer MJ, Hymas N, Levy R (1987) Platelet membrane properties in Alzheimer and multi-infarct dementias. Alzheimer Dis Assoc Disord 1:90–97

    Article  PubMed  CAS  Google Scholar 

  13. Kanfer JN, Hattori H, Oribel D (1986) Reduced phospholipase D activity in brain tissue samples from Alzheimer’s disease patients. Ann Neurol 20:265–267

    Article  PubMed  CAS  Google Scholar 

  14. Kanfer JN, McCartney DG (1986) Reduced phosphorylcholine hydrolysis by homoge-nates of temporal regions of Alzheimer’s brain. Biochem Biophys Res Commun 139:315–319

    Article  PubMed  CAS  Google Scholar 

  15. Khachaturian Z (1985) Diagnosis of Alzheimer’s disease. Arch Neurol 42:1097–1105

    PubMed  CAS  Google Scholar 

  16. Kish S, Karlinsky H, Becker L et al. (1989) Down’s syndrome individuals begin life with normal levels of brain cholinergic markers. J Neurochem 52:1183–1187

    Article  PubMed  CAS  Google Scholar 

  17. Lee HC, Blusztajn JK (1990) Glycerophosphocholine is the predominant metabolite of phosphatidylcholine in a human cholinergic cell line, LA-N-2. (American Society of Biochemistry and Molecular Biology meeting 1990, abstract no 2655)

    Google Scholar 

  18. Liscovitch M, Fresse A, Blusztajn KK, Wurtman RJ (1985) High performance liquid chromatography of water soluble choline metabolits. Anal Biochem 151:182–187

    Article  PubMed  CAS  Google Scholar 

  19. Maire J-C, Wurtman RJ (1985) Effect of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat stiatum. J Physiol (Paris) 80:189–195

    CAS  Google Scholar 

  20. 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

    PubMed  CAS  Google Scholar 

  21. Miatto O, Gonzalez G, Buonanno F, Growdon JH (1986) In vitro 31P NMR spectroscopy detects altered phospholipid metabolism in Alzheimer’s disease. Can J Neurol Sci 13:535–539

    PubMed  CAS  Google Scholar 

  22. Miatto O, Blusztajn JK, Logue M, Gonzalez G, Buonanno F, Growdon JH (1989) Detection of phospholipids in brain tissue using 31P NMR spectroscopy. In: Bazan NG, Horrocks LA, Toffano G (eds) Phospholipids in the nervous system: Biochemical and molecular pathology. Liviana, Padua, pp 243–250

    Google Scholar 

  23. Miller BL, Henden DJ, Cummings JF, Read S, Rice K, Benson DF (1986) Abnormal erythrocyte choline and influx in Alzheimer’s disease. Life Sci 38:485–490

    Article  PubMed  CAS  Google Scholar 

  24. Ogomori K, Kitamoto T, Tateishi J, Sato Y, Suetsugu M, Abe M (1989) β-Protein amyloid is widely distributed in the central nervous system of patients with Alzheimer’s disease. Am J Pathol 134:243–251

    PubMed  CAS  Google Scholar 

  25. Perry TL, Hansen S, Gandham SS (1981) Postmortem changes of amino compounds in human and rat brain. J Neurochem 36:406–412

    Article  PubMed  CAS  Google Scholar 

  26. Perry EK, Tomlinson BE, Blessed G, Bergman K, Gibson PH, Perry RH (1987) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 11:1457–1459

    Google Scholar 

  27. Peterson C, Goldman JE (1986) Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer’s donors. Proc Natl Acad Sci USA 83:2758–2762

    Article  PubMed  CAS  Google Scholar 

  28. Peterson C, Ratan RR, Shelanski ML, Goldman JE (1986) Cytosolic free calcium and cell spreading decrease in fibroblasts from aged and Alzheimer’s donors. Proc Natl Acad Sci USA 83:7999–8001

    Article  PubMed  CAS  Google Scholar 

  29. Pettegrew JW, Kopps J, Minshew NJ, Glonek T, Feliksik JM, Tow JP, Chohen MM (1987) 31P Nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: preliminary observations. J Neuropathol Exp Neurol 46:419–430

    Article  PubMed  CAS  Google Scholar 

  30. Pettegrew JW, Minshew NJ, Cohen MM, Kopp SJ, Glonek T (1984) 31P NMR changes in Alzheimer’s and Huntington’s disease brain. Neurology [Suppl 1] 34:281

    Google Scholar 

  31. Pettegrew JW, Moossy J, Withers G, McKeag D, Panchalingam K (1988) 31P Nuclear magnetic resonance study of the brain in Alzheimer’s disease. J Neuropathol Exp Neurol 47:235–248

    Article  PubMed  CAS  Google Scholar 

  32. Pettegrew JW, Panchalingam K, Moossy J, Martinez J, Rao G, Boller F (1988b) Correlation of phosphorus-31 magnetic resonance spectroscopy and morphologic findings in Alzheimer’s disease. Arch Neurol 45:1093–1096

    PubMed  CAS  Google Scholar 

  33. Rumble B, Retallack R, Hilbich C et al. (1989) Amyloid A4 protein and its precursor in Down’s syndrome and Alzheimer’s disease. N Engl J Med 320:1446–1452

    Article  PubMed  CAS  Google Scholar 

  34. Selkoe D (1989) Biochemistry of altered brain proteins in Alzheimer’s disease. Ann Rev Neurosci 12:463–490

    Article  PubMed  CAS  Google Scholar 

  35. Stokes CE, Hawthorne JN (1987) Reduced phosphoinositide concentrations in anterior temporal cortex of Alzheimer’s-diseased brains. J Neurochem 48:1018–1021

    Article  PubMed  CAS  Google Scholar 

  36. Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK (1989) Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res 484:217–227

    Article  PubMed  CAS  Google Scholar 

  37. Wurtman RJ, Blusztajn JK, Maire J-C (1985) „Autocannibalism“ of choline-containing membrane phospholipids in the pathogenesis of Alzheimer’s disease. Neurochem Int 7:369–372

    Article  PubMed  CAS  Google Scholar 

  38. Yates CM, Simpson J, Gordon A, Maloney AF, Allison Y, Ritchie LM, Urquhart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile-Alzheimer-type dementia and Down’s syndrome. Brain Res 280:119–126

    Article  PubMed  CAS  Google Scholar 

  39. Young LT, Kish SJ, Li PP, Warsh JJ (1988) Decreased brain [3H]inositol 1,4,5-trispho-sphate binding in Alzheimer’s disease. Neurosci Lett 94:198–202

    Article  PubMed  CAS  Google Scholar 

  40. Zubenko GS, Cohen BM, Growdon JH, Corkin S (1984) Cell membrane abnormality in patients with Alzheimer’s disease. Lancet 11:235

    Article  Google Scholar 

  41. Zubenko GS, Ferrell RE (1988) Monozygotic twins concordant for probable Alzheimer disease and increased platelet membrane fluidity. Am J Med Genet 29:431–436

    Article  PubMed  CAS  Google Scholar 

  42. Zubenko GS (1986) Hipoocampal membrane alteration in Alzheimer’s disease. Brain Res 385:115–121

    Article  PubMed  CAS  Google Scholar 

  43. Zubenko GS; Malinakova I, Chojnacki B (1987) Proliferation of internal membranes in platelets from patients with Alzheimer’s disease. J Neuropathol Exp Neurol 46:407–418

    Article  PubMed  CAS  Google Scholar 

  44. Zubenko GS, Wusylko M, Cohen BM, Boller F, Teply I (1987) Family study of platelet membrane fluidity in Alzheimer’s disease. Science 238:539–542

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. J. K. Blusztajn
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  2. J. H. Growdon
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  3. H.-C. Lee
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  4. M. Liscovitch
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  5. M. Logue
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  6. I. L. G-Coviella
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  7. C. Mauron
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  8. U. I. Richardson
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  9. I. Ulus
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  10. R. J. Wurtman
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Editors and Affiliations

  1. Psychiatrischen Klinik mit Poliklinik, Universität Erlangen-Nürnberg, Schwabachanlage 6-10, D-8520, Erlangen, Deutschland

    Eberhard Lungershausen (Direktor) (Direktor)

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© 1992 Springer-Verlag Berlin Heidelberg

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Blusztajn, J.K. et al. (1992). Phospholipide und Pathophysiologie bei der Alzheimer-Krankheit. In: Lungershausen, E. (eds) Demenz. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76932-0_8

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  • DOI: https://doi.org/10.1007/978-3-642-76932-0_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76933-7

  • Online ISBN: 978-3-642-76932-0

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