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Neurotransmitter Receptor Alterations in Alzheimer’s Disease

  • P. J. Whitehouse
  • K.-S. Au
Part of the Advances in Applied Neurological Sciences book series (NEUROLOGICAL, volume 2)

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized neuropathologically by senile plaques and neurofibrillary tangles occurring in association with dysfunction and eventual death of several specific neuronal populations. In brainstem and diencephalon, the neurotransmitter specificity of some affected populations of neurons is known. For example, the medial septum, nucleus of the diagonal band of Broca, and nucleus basalis of Meynert are components of the basal forebrain cholinergic system (Hedreen et al. 1984; Mesulam et al. 1984). In AD, dysfunction in this system (Whitehouse et al. 1981, 1982; Price et al. 1983) is the probable substrate for the loss of presynaptic cholinergic markers in the telencephalon (Bowen et al. 1976; Davies and Maloney 1976b). This cholinergic deficit has been linked to the severity of clinically apparent dementia and to the magnitude of neuropathologic changes (Blessed et al. 1968). In the brain-stem, neuronal dysfunction occurs in the noradrenergic locus ceruleus and serotonergic raphe nuclei (Forno 1978; Bondareff et al. 1982; Curcio and Kemper 1984). Loss of neurons also occurs in the amygdala, hippocampus, and neocortex, although the neurotransmitter specificity of these affected populations of neurons is less clear (Colon 1973; Terry et al. 1981; Ball 1977; Herzog and Kemper 1980; Hooper and Vogel 1976). Reductions in cortical somatostatin and gamma-aminobutyric acid (GABA) levels can probably be linked to dysfunction in populations of interneurons (Perry et al. 1977a; Davies et al. 1980; Rossor et al. 1980).

Keywords

Basal Forebrain Cholinergic Receptor Senile Dementia Neurotransmitter Receptor Locus Ceruleus 
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.

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References

  1. Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A qualitative study. Acta Neuropathol (Berl) 37: 111–118CrossRefGoogle Scholar
  2. Beal MF, Mazurek MF, Tran VT, Chattha G, Bird ED, Martin JB (1985) Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer’s disease. Science 229: 289–291PubMedCrossRefGoogle Scholar
  3. 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: 797–811PubMedCrossRefGoogle Scholar
  4. Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons or origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology (NY) 32: 164168Google Scholar
  5. Bowen DM, Flack RHA, White P, Smith CB, Davison AN (1974) Brain decarboxylase activities as indices of pathological change in senile dementia. Lancet 1: 1247–1249PubMedCrossRefGoogle Scholar
  6. Bowen DM, Smith CB, White P, Davison AN (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99: 459–496PubMedCrossRefGoogle Scholar
  7. Bowen DM, Spillane JA, Curzon G, Meier-Ruge W, White P, Goodhardt MJ, Iwangoff PO, Davison AN (1979) Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet 1: 11–14PubMedGoogle Scholar
  8. Bowen DM, Allen SJ, Benton JS, Goodhardt MJ, Haan EA, Palmer AM, Sims NR, Smith CCT, Spillane JA, Esiri MM, Neary D, Snowdon JS, Wilcock GK, Davison AN (1983a) Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer’s disease. J Neurochem 41: 266–272CrossRefGoogle Scholar
  9. Bowen DM, Davison AN, Sims NR (1983b) The cholinergic system in the ageing brain and dementia. In: Samuel D, Algeri S, Gershon S, Grimm VE, Toffano G (eds) Aging of the brain. Raven, New York, pp 183–190Google Scholar
  10. Caulfield MP, Straughan DW, Cross AI, Crow T, Birdsall NIM (1982) Cortical muscarinic receptor subtypes and Alzheimer’s Disease. Lancet 2: 1277PubMedCrossRefGoogle Scholar
  11. Colon EJ (1973) The cerebral cortex in presenil dementia. A quantitative analysis. Acta Neuropathol (Berl) 23: 281–290CrossRefGoogle Scholar
  12. Cross AJ, Crow TJ, Johnson JA, Perry EK, Perry RH, Blessed G, Tomlinson BE (1984a) Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type. J Neurol Sci 64: 109–117CrossRefGoogle Scholar
  13. Cross Ai, Crow TJ, Ferrier IN, Johnson JA, Bloom SR, Corsellis JAN (1984b) Serotonin receptor changes in dementia of the Alzheimer type. J Neurochem 43: 1574–1581CrossRefGoogle Scholar
  14. Curcio CA, Kemper T (1984) Nucleus raphe dorsalis in dementia of the Alzheimer type: neurofibrillary changes and neuronal packing density. J Neuropathol Exp Neurol 43: 359–368PubMedCrossRefGoogle Scholar
  15. Davies P, Feisullin S (1981) Postmortem stability of alpha-bungarotoxin binding sites in mouse and human brain. Brain Res 216: 449–454PubMedCrossRefGoogle Scholar
  16. Davies P, Maloney AJF (1976a) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2: 1403CrossRefGoogle Scholar
  17. Davies P, Maloney AJF (1976b) Selective loss of central cholinergic neurons in Alzheimer senile dementia. Nature 288: 279–280CrossRefGoogle Scholar
  18. Davies P, Verth AH (1978) Regional distribution of muscarinic acetylcholine receptor in normal and Alzheimer’s-type dementia brains. Brain Res 138: 385–392CrossRefGoogle Scholar
  19. Davies P, Katzman R, Terry RD (1980) Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia. Nature 288: 279–280PubMedCrossRefGoogle Scholar
  20. Drachman DB (1983) Myasthenia gravis: immunobiology of a receptor disorder. Trends Neurosci 6: 446–451CrossRefGoogle Scholar
  21. Forno LS (1978) The locus caeruleus in Alzheimer’s disease. J Neuropathol Exp Neurol 37: 614CrossRefGoogle Scholar
  22. Greenamyre JT, Penney JB, Young AB, D’Amato CJ, Hicks SP, Shoulson I (1985) Alterations in L-glutamate binding in Alzheimer’s and Huntington’s diseases. Science 227: 1496–1499PubMedCrossRefGoogle Scholar
  23. Hammer R, Berrie CP, Birdsall NJM, Burgen ASV, Hulme EC (1980) Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 283: 90–92PubMedCrossRefGoogle Scholar
  24. Hedreen JC, Struble RG, Whitehouse PJ, Price DL (1984) Topography of the magnocellular basal forebrain system in human brain. J Neuropathol Exp Neurol 43: 1–21PubMedCrossRefGoogle Scholar
  25. Herzog AG, Kemper TL (1980) Amygdaloid changes in aging and dementia. Arch Neurol 37: 625–629PubMedGoogle Scholar
  26. Hooper MW, Vogel FS (1976) The limbic system in Alzheimer’s disease. A neuropathologic investigation. Am J Pathol 85: 1–20Google Scholar
  27. Kuhar MJ (1985) Receptor localization with the microscope. In: Yamamura HI, Enna SJ, Kuhar MJ (eds) Neurotransmitter receptor binding, 2nd edn. Raven, New York, pp 153–176Google Scholar
  28. Lang W, Henke H (1983) Cholinergic receptor binding and autoradiography in brains of non-neurological and senile dementia of Alzheimer-type patients. Brain Res 267: 271–280PubMedCrossRefGoogle Scholar
  29. London ED, Waller SB (to be published) Relations between choline acetyltransferase and muscarinic binding in aging and Alzheimer’s disease. In: Hanin I (ed) Dynamics of cholinergic function. Plenum, New YorkGoogle Scholar
  30. Mash DS, Potter LT (1983) Changes in M1 and M2 muscarine receptors in Alzheimer’s disease and aging, and with lesions of cholinergic neurons in animals. Soc Neurosci Abstr 9: 582Google Scholar
  31. Mesulam M-M, Mufson EJ, Levey AI, Wainer BH (1984) Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Neuroscience 12: 669–686PubMedCrossRefGoogle Scholar
  32. Morley BJ, Kemp GE, Salvaterra P (1979) Alpha-bungarotoxin binding sites in the CNS. Life Sci 24: 859–872PubMedCrossRefGoogle Scholar
  33. Nordberg A, Larsson C, Adolfsson R, Alafuzoff I, Winblad B (1983) Muscarinic receptor compensation in hippocampus of Alzheimer patients. J Neural Transco 56: 13–19CrossRefGoogle Scholar
  34. Owen F, Poulter M, Waddington JL, Mashal RD, Crow TJ (1983) 3H-RO5–4864 and 3H-flunitrazepam binding in kainate-lesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type. Brain Res 278:373–375PubMedCrossRefGoogle Scholar
  35. Palacios JM (1982) Autoradiographic localization of muscarinic cholinergic reeptors in the hippocampus of patients with senile dementia. Brain Res 243: 173–175PubMedCrossRefGoogle Scholar
  36. Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE (1977a) Neurotransmitter enzyme abnormalities in senile dementia. J Neurol Sci 34: 247–265CrossRefGoogle Scholar
  37. Perry EK, Perry RH, Blessed G, Tomlinson BE (1977b) Necropsy evidence of central cholinergic deficits in senile dementia. Lancet 1: 189CrossRefGoogle Scholar
  38. Price DL, Whitehouse PJ, Struble RG, Price DL Jr, Cork LC, Hedreen JC, Kitt CA (1983) Basal forebrain cholinergic neurons and neuritic plaques in primate brain. Biological aspects of Alzheimer’s disease. Banbury Rep 15: 65–77Google Scholar
  39. Reisine TD, Yamamura HI, Bird ED, Spokes E, Enna SJ (1978) Pre-and postsynaptic neuro-chemical alterations in Alzheimer’s disease. Brain Res 159: 477–481PubMedCrossRefGoogle Scholar
  40. Rinne JO, Rinne JK, Laakso K, Paijarvi L, Rinne UK (1984) Reduction in muscarinic receptor binding in limbic areas of Alzheimer brain. J Neurol Neurosurg Psychiatry 47: 651–653PubMedCrossRefGoogle Scholar
  41. Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL (1980) Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type. Neurosci Lett 20: 373–377PubMedCrossRefGoogle Scholar
  42. Terry RD, Peck A, DeTeresa R, Schechter R, Horoupian DS (1981) Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 10: 184–192PubMedCrossRefGoogle Scholar
  43. Troncoso JC, Cork LC, Whitehouse PJ, Kuhar MJ, Price DL (1984) Canine inherited ataxia: neurotransmitter receptors in the cerebellum. Ann Neurol 16: 135CrossRefGoogle Scholar
  44. Unnerstall JR, Kuhar MJ, Niehoff DL, Palacios JM (1981) Benzodiazepine receptors are coupled to a subpopulation of gamma-aminobutyric acid (GABA) receptors: evidence from a quantitative autoradiographic study. J Pharmacol Exp Ther 218: 797–804PubMedGoogle Scholar
  45. Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, Frost II, Ravert HT, Links JM, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ (1983) Imaging dopamine receptors in the human brain by positron tomography. Science 221: 1264–1266PubMedCrossRefGoogle Scholar
  46. White P, Goodhardt MJ, Keet JP, Hiley CR, Carrasco LH, Williams IEI, Bowen DM (1977) Neocortical cholinergic neurons in elderly people. Lancet 1: 668–670PubMedCrossRefGoogle Scholar
  47. Whitehouse PJ (to be published) Receptor autoradiography: applications in neuropathology. Trends NeurosciGoogle Scholar
  48. Whitehouse PI, Price DL, Clark AW, Coyle JT, DeLong MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10: 122–126PubMedCrossRefGoogle Scholar
  49. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237–1239PubMedCrossRefGoogle Scholar
  50. Whitehouse PJ, Jones BE, Kopajtic TA, Price DL, Kuhar MJ (1984a) Receptors in the nucleus basalis of primates: an in vitroautoradiographic study. Ann Neurol 16: 118Google Scholar
  51. Whitehouse Pi, Lynch D, Kuhar MJ (1984b) Effects of postmortem delay and temperature on neurotransmitter receptor binding in a rat model of the human autopsy process. J Neurochem 43: 553–559CrossRefGoogle Scholar
  52. Whitehouse Pi, Martino AM, Price DL, Kellar KJ (1985) Reductions in nicotinic but not muscarinic cholinergic receptors in Alzheimer’s disease measured using [3H]acetylcholine. Ann Neurol 18: 145CrossRefGoogle Scholar
  53. Whitehouse PI, Trifiletti RR, Jones BE, Folstein S, Price DL, Snyder SH, Kuhar MJ (to be publisheda) Neurotransmitter receptor alterations in Huntington’s disease: autoradiographic and homogenate studies with special reference to benzodiazepine receptor complexes. Ann NeurolGoogle Scholar
  54. Whitehouse PI, Kopajtic T, Jones BE, Kuhar MJ, Price DL (to be publishedb) An in vitroreceptor autoradiographic study of muscarinic cholinergic receptor subtypes in the amygdala and neocortex of patients with Alzheimer’s disease. Meeting of the American Academy of Neurology, 1985Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • P. J. Whitehouse
    • 1
  • K.-S. Au
    • 2
  1. 1.Departments of Neurology and NeuroscienceNeuropathology LaboratoryUSA
  2. 2.Division of Geriatrics, Department of MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA

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