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Nicotinic binding sites in cerebral cortex and hippocampus in alzheimer's dementia

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Abstract

Postmortem cerebral neocortical and hippocampal samples were taken from patients who died with dementia of the Alzheimer type (DAT) and individuals without diagnoses of neurological or psychiatric disease (control). Nicotinic binding was assayed with 20 nM [3H]acetylcholine ([3H]ACh) in the presence of atropine, or with 4 nM (-)-[3H]Nic). Binding of both ligands was lower in the following regions from DAT vs. control brains (P≤0.05): superior, middle and inferior temproal gyri, orbital frontal gyrus, middle frontal gyrus, pre- and postcentral gyri, inferior parietal lobule, and hippocampal endplate. Values of the correlation coefficient (r's) for binding of the nicotinic cholinergic ligands in these regions ranged from 0.70 to 0.93 (P's<0.05), suggesting that [3H]ACh and (-)-[3H]Nic labeled the same sites in human brain. There was no difference in nicotinic binding in the presubiculum, comparing DAT and control samples (P>0.05). Here too, correlations between binding of the two ligands were statistically significant in control and DAT groups (r's=0.92,P's<0.05). Nicotinic binding measured with [3H]ACh, but not (-)-[3H]Nic, was significantly lower in the H2 (field of Rose) and H1-subiculum areas of DAT samples compared to control. Correlations between binding of the two ligands in these regions ranged from 0.21 to 0.34 for the two groups (P's>0.05). The findings support a loss of neocortical and hippocampal nicotininc cholinergic binding sites in DAT. Further study is necessary to better characterize the regional losses of nicotinic binding in DAT and to resolve the differences in binding measured by [3H]ACh and (-)-[3H]Nic in the H1-subiculum and H2 (field of Rose) regions.

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References

  1. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E. 1984. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services task force on Alzheimer's disease. Neurology 34:939–944.

    PubMed  Google Scholar 

  2. Perry, E. K., Gibson, P. H., Blessed, G., Perry, R., and Tomlinson, B. E. 1977. Neurotransmitter enzyme abonormalities in senile dementia: Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J. Neurol. Sci. 34:247–265.

    PubMed  Google Scholar 

  3. Terry, R., and Davies, P. 1980. Dementia of the Alzheimer type. Ann. Rev. Neurosci. 3:77–95.

    PubMed  Google Scholar 

  4. Terry, E. 1980. The cholinergic system in old age and Alzheimer's disease. Age and Ageing 9:1–8.

    PubMed  Google Scholar 

  5. Price, D., Whitehouse, P., Struble, R., Clark, A., Coyle, A., DeLong, M., and Hedreen, J. 1982. Basal forebrain cholinergic systems in Alzheimer's disease and related dementias. Neurosci. Commentaries 1:84–92.

    Google Scholar 

  6. Rinne J., Laakso, K., Lonnberg, P., Molsa, P., Paljarvi, L., Rinne, J., Sako, E., and Rinne, U. 1985. Brain muscarinic receptors in senile dementia. Brain Res 336:19–25.

    PubMed  Google Scholar 

  7. Rossor, M. 1982. Dementia. Lancet II:1200–1204.

    Google Scholar 

  8. Perry, E. and Perry, R. 1980. The cholinergic system in Alzheimer's disease. Pages 135–183,in Roberts P. (ed.), Biochemistry of Dementia. John Wiley and Sons, New York.

    Google Scholar 

  9. Wilcock, F. G., Esiri, M., Bowen, D., and Smith, C. 1982. Alzheimer's disease: Correlation of cortical choline acetyltransferase activity with the severity of dementia and histologial abnormalities. J. Neurol. Sci. 57:407–417.

    PubMed  Google Scholar 

  10. Ball, M., Merskey, H., Fisman, M., Fyfe, I., Fox, H., Cape, R., Waller, S., and London, E. 1983. Hippocampal morphometry in Alzheimer dementia: Implications for neurochemical hypothesis. Pages 45–57,in Katzman, R. (ed.), Banbury Report 15: Biological Aspects of Alzheimer's Disease. Cold Spring Harbor Laboratories, Long Island, N.Y.

    Google Scholar 

  11. Bowen, D., White, P., Spillane, J., Goodhardt, M., Curzon, G., Iwangoff, P., Meier-Ruge, W., and Davison, A. 1979. Accelerated aging or selective neuronal loss as an important cause of dementia. Lancet I:11–14.

    Google Scholar 

  12. Perry, E. K., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P. H., and Perry, R. H. 1978. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br. Med. J. II:1457–1459.

    Google Scholar 

  13. Caulfield, M., Straughan, D., Cross, A., Crow, T., and Birdsall, N. 1982. Cortical muscarinic receptor subtypes and Alzheimer's disease. Lancet II:1277.

    Google Scholar 

  14. Davies, P. and Verth, A. 1977. Regional distribution of muscarinic acetylcholine receptor in normal and Alzheimer's type dementia brains. Brain Res. 138:385–392.

    PubMed  Google Scholar 

  15. Gottfries, C-G., Adolfsson, R., Aquilonius, S-M. Carlsson, A., Eckernas, S-A., Nordberg, A., Oreland, L., Svennerholm, L., Wiberg, A., and Winblad, B. 1983. Biochemical changes in dementia disorders of Alzheimer type. Neurobiol. Aging 4:261–271.

    PubMed  Google Scholar 

  16. Lang, W. and Henke, H. 1983. Cholinergic receptor binding and autoradiography in brains of non-neurological and senile dementia of the Alzheimer-type patients. Brain Res. 267:271–280.

    PubMed  Google Scholar 

  17. Nordberg, A., Larsson, C., Adolfsson, R., Alafuzoff, I., and Winblad, B. 1983. Muscarinic receptor compensation in hippocampus of Alzheimer patients. J. Neural Transm. 56:13–19.

    PubMed  Google Scholar 

  18. Palacios, J. 1982. Autoradiographic localization of muscarinic cholinergic receptors in the hippocampus of patients with senile dementia. Brain Res. 243:173–175.

    PubMed  Google Scholar 

  19. Waller, S., Ball, M., Reynolds, M., and London, E. 1986. Muscarinic binding and choline acetyltransferase in postmortem brains of demented patients. Can. J. Neurol. Sci. 13S:528–532.

    Google Scholar 

  20. Araujo, D. M., Lapchak, P. A., Robitaille, Y., Gauthier, S., and Quirion, R. 1988. Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease. J. Neurochem. 50:1914–1923.

    PubMed  Google Scholar 

  21. Holman, B. L., Gibson, R. E., Hill, T. C., Eckelman, W. C., Albert, M., and Reba, R. C. 1985. Muscarinic acetylcholine receptors in Alzheimer's disease:In vivo imaging with iodine 125-labeled 3-quinuclidinyl-4-iodobenzilate with emission tomography. JAMA 254:3063–3066.

    PubMed  Google Scholar 

  22. Mash, D., Flynn, D., and Potter, L. 1985. Loss of M2 muscarinic receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 228:1115–1117.

    PubMed  Google Scholar 

  23. Nordberg, A., Alafuzoff, I., and Winblad, B. 1986. Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type. Neurosci. Letters 70:160–164.

    Google Scholar 

  24. Reisine, T., Yamamura, H., Bird, E., Spokes, E., and Enna, S. 1978. Pre- and postsynaptic neurochemical alterations in Alzheimer's disease. Brain Res. 159:477–481.

    PubMed  Google Scholar 

  25. Rinne, J., Rinne, J., Laakso, K., Paljarvi, L., and Rinne, U. 1984. Reduction in muscarinic receptor binding in limbic areas of Alzheimer's brain. J. Neurol. Neurosurg. Psychiatry 47:651–652.

    PubMed  Google Scholar 

  26. Jenni-Eirmann, S., vonHahn, H. P., Honegger, C. G., and Ulrich, J. 1984. Studies on neurotransmitter binding in senile dementia. Gerontology 30:350–358.

    PubMed  Google Scholar 

  27. Nordberg, A., Adem, A., Nilsson, L., and Winblad, B. 1987. Cholinergic deficits in CNS and peripheral non-neuronal tissue in Alzheimer's dementia. Pages 858–868,in Dowdall M. (ed.), Cellular and Molecular Basis of Cholinergic Function. Ellis Howard Publishers, Sussex, England.

    Google Scholar 

  28. Kellar, K. J., Whitehouse, P. J., Martino-Barrows, A. M., Marcus, K., and Price, D. L. 1987. Muscarinic and nicotinic cholinergic binding sites in Alzheimer's disease cerebral cortex. Brain Research 436:62–68.

    PubMed  Google Scholar 

  29. Nordberg, A. and Winblad, B. 1986. Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains. Neurosci. Letters 72:115–119.

    Google Scholar 

  30. Shimohama, S., Taniguchi, T., Fujiwara, M., and Kameyama, M. 1986. Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia. J. Neurochem. 46:288–293.

    PubMed  Google Scholar 

  31. Whitehouse, P. J., Martino, A. M., Antuono, P. G., Lowenstein, P. R., Coyle, J. T., Price, D. L., and Kellar, K. J. 1986. Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Research 371:146–151.

    PubMed  Google Scholar 

  32. Whitehouse, P. J., Martino, A. M., Wagster, M. V., Price, D. L., Mayeux, R., Atack, J. R., and Kellar, K. J. 1988. Reductions in [3H]nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: An autoradiographic study. Neurology 38:720–723.

    PubMed  Google Scholar 

  33. Khachaturian, Z. S. Diagnosis of Alzheimer's disease. Arch. Neurol. 42:1097–1105.

  34. Ball, M. J., Griffin-Brooks, S., MacGregor, J., Nagy, B., Ojalvo-Rose, E., and Fewster, P. H. 1988. Neuropathological definition of Alzheimer's disease: Multivariate analyses in the morphometric distinction between Alzheimer dementia and normal aging. Alzheimer Dis. Assoc. Disorders 2:29–37.

    Google Scholar 

  35. Ball, M. J. 1978. Histotopography of cellular changes in Alzheimer's disease. Pages 89–104,in Nandy K. (ed.), Senile dementia: A biomedical approach. Elsevier Science Publishers, New York.

    Google Scholar 

  36. Schwartz, R. D. and Kellar, K. J. 1983. Nicotinic cholinergic receptor binding sites in the brain: Regulationin vivo. Science 220:214–216.

    PubMed  Google Scholar 

  37. Schwartz, R. D., McGee, Jr., E., and Kellar, K. J. 1982. Nicotinic cholinergic receptors labeled by [3H]acetylcholine in rat brain. Mol. Pharmacol. 22:56–62.

    PubMed  Google Scholar 

  38. Davies, P. and Feisullin, S. 1981. Postmortem stability of α-bungarotoxin binding sites in mouse and human brain. Brain Res. 216:449–454.

    PubMed  Google Scholar 

  39. Morley, B. J., Kemp, G. E., and Salvaterra, P. 1979. Alpha-bungarotoxin binding sites in the CNS. Life Sci. 24:859–872.

    PubMed  Google Scholar 

  40. Oswald, R. E. and Freeman, J. A. 1981. Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors. Neuroscience 6:1–14.

    PubMed  Google Scholar 

  41. Clarke, P. B. S., Schwartz, R. D., Paul, S. M. Pert, C. B., and Pert, A. 1985. Nicotinic binding in rat brain. Autoradiographic comparison of [3H]acetylcholine, [3H]nicotine and [125I]-alpha-bungarotoxin. J. Neurosci. 5:1307–1315.

    PubMed  Google Scholar 

  42. Larsson, C. and Nordberg, A. 1985. Comparative analysis of nicotine-like receptor-ligand interactions in rodent brain homogenate. J. Neurochem. 45:24–31.

    PubMed  Google Scholar 

  43. Marks, M. J. and Collins, A. C. 1982. Characterization of nicotinic binding in mouse brain and comparison with the binding of alpha-bungarotoxin and quinuclidinyl benzilate. Mol. Pharmacol. 22:554–564.

    PubMed  Google Scholar 

  44. Abood, D. M. and Grassi, S. 1986. [3H]Methylcarbamylcholine, a new radioligand for studying brain nicotinic receptors. Biochem. Pharmacol. 35:4199–4202.

    Google Scholar 

  45. Larsson, C., Nilsson, L., Halén, A. and Nordberg, A. 1986. Subchronic treatment of rats with nicotine: Effects on tolerance and on [3H]acetylcholine and [3H]nicotine binding in the brain. Drug Alc. Depend. 17:37–45.

    Google Scholar 

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Authors and Affiliations

  1. Neuropharmacology Laboratory, Addiction Research Center, National Institute on Drug Abuse, P.O. Box 5180, 21224, Baltimore, MD

    Edythe D. London

  2. Departments of Pathology, Clinical Neurological Sciences and Psychiatry and the Atkinson Neurobiology of Aging Unit, University of Western Ontario, N6A 5C1, London, Canada

    Melvyn J. Ball

  3. Department of Physiology and Pharmacology, University of South Dakota School of Medicine, 57069-2390, Vermillion, SD

    Steven B. Waller

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  1. Edythe D. London
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London, E.D., Ball, M.J. & Waller, S.B. Nicotinic binding sites in cerebral cortex and hippocampus in alzheimer's dementia. Neurochem Res 14, 745–750 (1989). https://doi.org/10.1007/BF00964952

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