Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1988 Apr;51(4):544–548. doi: 10.1136/jnnp.51.4.544

Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy.

S J Kish 1, L Schut 1, J Simmons 1, J Gilbert 1, L J Chang 1, M Rebbetoy 1
PMCID: PMC1032971  PMID: 3164041

Abstract

The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less severe change (-37%) in the hippocampus. The magnitude of the enzyme reduction in cerebral cortex was equal to or greater than that reported in brain of demented Alzheimer's and Parkinson's disease patients having loss of AChE-containing nucleus basalis cholinergic neurons. It is concluded that the data provide additional biochemical evidence suggesting a cerebral cortical cholinergic denervation in OPCA.

Full text

PDF
544

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atack J. R., Perry E. K., Bonham J. R., Candy J. M., Perry R. H. Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system. J Neurochem. 1986 Jul;47(1):263–277. doi: 10.1111/j.1471-4159.1986.tb02858.x. [DOI] [PubMed] [Google Scholar]
  2. Atack J. R., Perry E. K., Bonham J. R., Perry R. H., Tomlinson B. E., Blessed G., Fairbairn A. Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form. Neurosci Lett. 1983 Sep 30;40(2):199–204. doi: 10.1016/0304-3940(83)90302-6. [DOI] [PubMed] [Google Scholar]
  3. Bartus R. T., Dean R. L., 3rd, Beer B., Lippa A. S. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982 Jul 30;217(4558):408–414. doi: 10.1126/science.7046051. [DOI] [PubMed] [Google Scholar]
  4. Bonham J. R., Gowenlock A. H., Timothy J. A. Acetylcholinesterase and butyrylcholinesterase measurement in the pre-natal detection of neural tube defects and other fetal malformations. Clin Chim Acta. 1981 Sep 10;115(2):163–170. doi: 10.1016/0009-8981(81)90072-3. [DOI] [PubMed] [Google Scholar]
  5. Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res. 1979 Aug 3;171(2):319–327. doi: 10.1016/0006-8993(79)90336-6. [DOI] [PubMed] [Google Scholar]
  6. DeKosky S. T., Scheff S. W., Markesbery W. R. Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer's disease and aging. Neurology. 1985 Oct;35(10):1425–1431. doi: 10.1212/wnl.35.10.1425. [DOI] [PubMed] [Google Scholar]
  7. ELLMAN G. L., COURTNEY K. D., ANDRES V., Jr, FEATHER-STONE R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961 Jul;7:88–95. doi: 10.1016/0006-2952(61)90145-9. [DOI] [PubMed] [Google Scholar]
  8. Fibiger H. C. The organization and some projections of cholinergic neurons of the mammalian forebrain. Brain Res. 1982 Nov;257(3):327–388. doi: 10.1016/0165-0173(82)90011-x. [DOI] [PubMed] [Google Scholar]
  9. Fonnum F. A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem. 1975 Feb;24(2):407–409. doi: 10.1111/j.1471-4159.1975.tb11895.x. [DOI] [PubMed] [Google Scholar]
  10. Haines J. L., Schut L. J., Weitkamp L. R., Thayer M., Anderson V. E. Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies. Neurology. 1984 Dec;34(12):1542–1548. doi: 10.1212/wnl.34.12.1542. [DOI] [PubMed] [Google Scholar]
  11. Kan K. S., Chao L. P., Forno L. S. Immunohistochemical localization of choline acetyltransferase in the human cerebellum. Brain Res. 1980 Jul 7;193(1):165–171. doi: 10.1016/0006-8993(80)90953-1. [DOI] [PubMed] [Google Scholar]
  12. Kanazawa I., Kwak S., Sasaki H., Mizusawa H., Muramoto O., Yoshizawa K., Nukina N., Kitamura K., Kurisaki H., Sugita K. Studies on neurotransmitter markers and neuronal cell density in the cerebellar system in olivopontocerebellar atrophy and cortical cerebellar atrophy. J Neurol Sci. 1985 Dec;71(2-3):193–208. doi: 10.1016/0022-510x(85)90059-0. [DOI] [PubMed] [Google Scholar]
  13. Kish S. J., Currier R. D., Schut L., Perry T. L., Morito C. L. Brain choline acetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy. Ann Neurol. 1987 Aug;22(2):272–275. doi: 10.1002/ana.410220214. [DOI] [PubMed] [Google Scholar]
  14. Konigsmark B. W., Weiner L. P. The olivopontocerebellar atrophies: a review. Medicine (Baltimore) 1970 May;49(3):227–241. doi: 10.1097/00005792-197005000-00003. [DOI] [PubMed] [Google Scholar]
  15. Landis D. M., Rosenberg R. N., Landis S. C., Schut L., Nyhan W. L. Olivopontocerebellar degeneration. Clinical and ultrastructural abnormalities. Arch Neurol. 1974 Nov;31(5):295–307. doi: 10.1001/archneur.1974.00490410043003. [DOI] [PubMed] [Google Scholar]
  16. McGeer E. G., McGeer P. L., Kamo H., Tago H., Harrop R. Cortical metabolism, acetylcholinesterase staining and pathological changes in Alzheimer's disease. Can J Neurol Sci. 1986 Nov;13(4 Suppl):511–516. doi: 10.1017/s0317167100037227. [DOI] [PubMed] [Google Scholar]
  17. Meier-Ruge W., Iwangoff P., Reichlmeier K. Neurochemical enzyme changes in Alzheimer's and Pick's disease. Arch Gerontol Geriatr. 1984 Jul;3(2):161–165. doi: 10.1016/0167-4943(84)90007-4. [DOI] [PubMed] [Google Scholar]
  18. Mesulam M. M., Mufson E. J., Levey A. I., Wainer B. H. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol. 1983 Feb 20;214(2):170–197. doi: 10.1002/cne.902140206. [DOI] [PubMed] [Google Scholar]
  19. Perry E. K., Perry R. H., Smith C. J., Purohit D., Bonham J., Dick D. J., Candy J. M., Edwardson J. A., Fairbairn A. Cholinergic receptors in cognitive disorders. Can J Neurol Sci. 1986 Nov;13(4 Suppl):521–527. doi: 10.1017/s0317167100037240. [DOI] [PubMed] [Google Scholar]
  20. Perry E. K. The cholinergic hypothesis--ten years on. Br Med Bull. 1986 Jan;42(1):63–69. doi: 10.1093/oxfordjournals.bmb.a072100. [DOI] [PubMed] [Google Scholar]
  21. Rich S. S., Wilkie P., Schut L., Vance G., Orr H. T. Spinocerebellar ataxia: localization of an autosomal dominant locus between two markers on human chromosome 6. Am J Hum Genet. 1987 Oct;41(4):524–531. [PMC free article] [PubMed] [Google Scholar]
  22. Rossor M. N., Garrett N. J., Johnson A. L., Mountjoy C. Q., Roth M., Iversen L. L. A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain. 1982 Jun;105(Pt 2):313–330. doi: 10.1093/brain/105.2.313. [DOI] [PubMed] [Google Scholar]
  23. Ruberg M., Rieger F., Villageois A., Bonnet A. M., Agid Y. Acetylcholinesterase and butyrylcholinesterase in frontal cortex and cerebrospinal fluid of demented and non-demented patients with Parkinson's disease. Brain Res. 1986 Jan 1;362(1):83–91. doi: 10.1016/0006-8993(86)91401-0. [DOI] [PubMed] [Google Scholar]
  24. Sims N. R., Bowen D. M., Davison A. N. [14C]acetylcholine synthesis and [14C]carbon dioxide production from [U-14C]glucose by tissue prisms from human neocortex. Biochem J. 1981 Jun 15;196(3):867–876. doi: 10.1042/bj1960867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Struble R. G., Lehmann J., Mitchell S. J., McKinney M., Price D. L., Coyle J. T., DeLong M. R. Basal forebrain neurons provide major cholinergic innervation of primate neocortex. Neurosci Lett. 1986 May 15;66(2):215–220. doi: 10.1016/0304-3940(86)90193-x. [DOI] [PubMed] [Google Scholar]
  26. Tagliavini F., Pilleri G. Neuronal loss in the basal nucleus of Meynert in a patient with olivopontocerebellar atrophy. Acta Neuropathol. 1985;66(2):127–133. doi: 10.1007/BF00688687. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES