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. 1991 Sep;54(9):832–835. doi: 10.1136/jnnp.54.9.832

Cerebrospinal fluid acetylcholinesterase in progressive supranuclear palsy: reduced activity relative to normal subjects and lack of inhibition by oral physostigmine.

J R Atack 1, I Litvan 1, L J Thal 1, C May 1, S I Rapoport 1, T N Chase 1
PMCID: PMC1014527  PMID: 1955905

Abstract

Acetylcholinesterase (AChE) activity was measured in lumbar cerebrospinal fluid (CSF) of 11 patients with progressive supranuclear palsy (PSP) and 18 age-matched healthy control subjects. Mean CSF AChE activity in PSP subjects was significantly reduced by 31% relative to control subjects (p less than 0.002). In the light of evidence of a central cholinergic deficit, physostigmine was administered orally (0.5-2.0 mg every two hours, six times a day for 10 days) to eight of the 11 PSP patients. CSF was sampled when the patients were on placebo and when receiving physostigmine and CSF AChE and butyrylcholinesterase (BChE) activities were measured. There was no significant change in either CSF AChE or BChE activities following physostigmine treatment. These data suggest that the doses of physostigmine used were insufficient to produce marked inhibition of AChE within the central nervous system.

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Selected References

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

  1. Atack J. R., May C., Kaye J. A., Kay A. D., Rapoport S. I. Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type. Ann Neurol. 1988 Feb;23(2):161–167. doi: 10.1002/ana.410230209. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Atack J. R., Yu Q. S., Soncrant T. T., Brossi A., Rapoport S. I. Comparative inhibitory effects of various physostigmine analogs against acetyl- and butyrylcholinesterases. J Pharmacol Exp Ther. 1989 Apr;249(1):194–202. [PubMed] [Google Scholar]
  4. Hirsch E. C., Graybiel A. M., Duyckaerts C., Javoy-Agid F. Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5976–5980. doi: 10.1073/pnas.84.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kish S. J., Chang L. J., Mirchandani L., Shannak K., Hornykiewicz O. Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. Ann Neurol. 1985 Nov;18(5):530–536. doi: 10.1002/ana.410180504. [DOI] [PubMed] [Google Scholar]
  6. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  7. Litvan I., Gomez C., Atack J. R., Gillespie M., Kask A. M., Mouradian M. M., Chase T. N. Physostigmine treatment of progressive supranuclear palsy. Ann Neurol. 1989 Sep;26(3):404–407. doi: 10.1002/ana.410260318. [DOI] [PubMed] [Google Scholar]
  8. Oyanagi K., Takahashi H., Wakabayashi K., Ikuta F. Selective decrease of large neurons in the neostriatum in progressive supranuclear palsy. Brain Res. 1988 Aug 23;458(2):218–223. doi: 10.1016/0006-8993(88)90464-7. [DOI] [PubMed] [Google Scholar]
  9. Parent A., Csonka C., Etienne P. The occurrence of large acetylcholinesterase-containing neurons in human neostriatum as disclosed in normal and Alzheimer-diseased brains. Brain Res. 1984 Jan 16;291(1):154–158. doi: 10.1016/0006-8993(84)90663-2. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Ruberg M., Javoy-Agid F., Hirsch E., Scatton B., LHeureux R., Hauw J. J., Duyckaerts C., Gray F., Morel-Maroger A., Rascol A. Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol. 1985 Nov;18(5):523–529. doi: 10.1002/ana.410180503. [DOI] [PubMed] [Google Scholar]
  12. Saper C. B., Loewy A. D. Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry. Brain Res. 1982 Dec 9;252(2):367–372. doi: 10.1016/0006-8993(82)90404-8. [DOI] [PubMed] [Google Scholar]
  13. Sharpless N. S., Thal L. J. Plasma physostigmine concentrations after oral administration. Lancet. 1985 Jun 15;1(8442):1397–1398. doi: 10.1016/s0140-6736(85)91827-6. [DOI] [PubMed] [Google Scholar]
  14. Somani S. M., Khalique A. Pharmacokinetics and pharmacodynamics of physostigmine in the rat after intravenous administration. Drug Metab Dispos. 1987 Sep-Oct;15(5):627–633. [PubMed] [Google Scholar]
  15. Tagliavini F., Pilleri G., Gemignani F., Lechi A. Neuronal loss in the basal nucleus of Meynert in progressive supranuclear palsy. Acta Neuropathol. 1983;61(2):157–160. doi: 10.1007/BF00697397. [DOI] [PubMed] [Google Scholar]
  16. Thal L. J., Lasker B., Sharpless N. S., Bobotas G., Schor J. M., Nigalye A. Plasma physostigmine concentrations after controlled-release oral administration. Arch Neurol. 1989 Jan;46(1):13–13. doi: 10.1001/archneur.1989.00520370015007. [DOI] [PubMed] [Google Scholar]
  17. Thal L. J., Masur D. M., Sharpless N. S., Fuld P. A., Davies P. Acute and chronic effects of oral physostigmine and lecithin in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(3-5):627–636. doi: 10.1016/0278-5846(86)90032-1. [DOI] [PubMed] [Google Scholar]
  18. Whelpton R., Hurst P. Bioavailability of oral physostigmine. N Engl J Med. 1985 Nov 14;313(20):1293–1294. doi: 10.1056/NEJM198511143132016. [DOI] [PubMed] [Google Scholar]
  19. Whitehouse P. J., Kellar K. J. Nicotinic and muscarinic cholinergic receptors in Alzheimer's disease and related disorders. J Neural Transm Suppl. 1987;24:175–182. [PubMed] [Google Scholar]
  20. Young A. B. Progressive supranuclear palsy: postmortem chemical analysis. Ann Neurol. 1985 Nov;18(5):521–522. doi: 10.1002/ana.410180502. [DOI] [PubMed] [Google Scholar]

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