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Activities and Kinetic Properties of Lumbar Cerebrospinal Fluid Cholinesterases in Relation to Clinical Diagnosis, Severity, and Progression of Alzheimer's Disease

Published online by Cambridge University Press:  18 September 2015

F. Jacob Huff*
Affiliation:
Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
Clara T. Reiter
Affiliation:
Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
Jack Protetch
Affiliation:
Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine
*
Neuroscience Research Group, Hoechst-Roussel Pharmaceuticals, Routes 202-206, Building M-338, Somerville, N.J., USA 08876
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Abstract:

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Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of lumbar cerebrospinal fluid (CSF) have been measured in seventeen patients with a clinical diagnosis of probable Alzheimer's disease (Prob AD), possible Alzheimer's disease (Poss AD), or dementia of non-Alzheimer aetiology (Non-AD). The three diagnostic groups did not differ with regard to the Km or saturation kinetic properties of AChE and BChE. The CSF AChE activity was significantly higher in Prob AD than in Non-AD patients. The groups did not differ significantly in BChE activity. The ratio of AChE to BChE activity was significantly higher in both the Prob AD and Poss AD groups than in the Non-AD group, and the ranges of values in the Prob AD and Non-AD groups did not overlap. Among patients in the Prob AD group, severity of dementia was correlated with both AChE activity and the AChE/BChE ratio, and progression of dementia over time was also correlated with AChE/BChE.

The AChE/BChE ratio correlated more strongly than AChE with severity and progression of dementia in Prob AD patients, and also better distinguished them from Non-AD patients, suggesting that AChE/BChE may be the more useful marker for diagnosis of AD. It is not clear from the results whether AChE/BChE is useful for diagnosis of the complex dementia cases in the Poss AD group.

Résumé:

RÉSUMÉ:

L'activité de l'acétyl-cholinestérase (AChE) et de la butyrylcholinestérase (BChE) du liquide céphalo-rachidien (LCR) lombaire ont été mesurées chez dix-sept patients avec un diagnostic de maladie d'Alzheimer probable (Prob MA), maladie d'Alzheimer possible (Poss MA), ou démence d'étiologie autre (Non-MA). Les trois groupes de patients ne différaient pas quant au Km ou auz propriétés cinétiques de saturation de l'AChE et de la BChE. L'activité de l'AChE dans le LCR était significativement plus élevée chez les Prob MA que chez les Non-MA. Les deux groupes ne différaient pas significativement quant à l'activité de la BChE. Le rapport entre l'activité AChE et l'activité BChE était significativement plus élevé dans les groupes Prob MA et Poss MA que dans le groupe Non-MA, et l'écart des valeurs dans les groupes Prob MA et Non-MA ne se chevauchaient pas. Parmi les patients du groupe Prob MA, la sévérité de la démence était en corrélation avec l'activité de l'AChE et le rapport AChE/BChE, et la progression de la démence dans le temps était également en corrélation avec l'activité de l'AChE et le rapport AChE/BChE, et la progression de la démence dans le temps était également en corrélation avec l'AChE/BChE.

La corrélation entre le rapport AChE/BChE et la sévérité et la progression de la démence chez les patients Prob MA était plus forte que celle de l'AChE et les distinguait mieux des patients Non-MA, suggérant que l'AChE/BChE peut être le marqueur le plus utile pour le diagnostic de la MA. Ces résultats ne nous permettent pas de déterminer si l'AChE/BChE est utile dans le diagnostic des cas complexes de deménce du groupe Poss MA.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

References

REFERENCES

1. Perry, EK, Tomlinson, BE, Blessed, G, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Brit Med J 1987; 2: 14571459.Google Scholar
2. Bowen, DM, Smith, CB, White, P, et al. Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 1976; 99: 459496.Google Scholar
3. Rossor, MN, Garrett, NJ, Johnson, AL, et al. A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain 1982; 105: 313330.CrossRefGoogle ScholarPubMed
4. Perry, EK, Perry, RH, Blessed, G, et al. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol Appl Neurobiol 1978; 4: 273277.CrossRefGoogle ScholarPubMed
5. Soininen, HS, Jolkkonen, JT, Reinikainen, KJ, et al. Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of the Alzheimer type. J Neurol Sci 1984; 63: 167172.Google Scholar
6. Arendt, T, Bigl, V, Walther, F, et al. Decreased ratio of CSF acetylcholinesterase to butyrylcholinesterase activity in Alzheimer’s disease. Lancet 1984; 1: 173.CrossRefGoogle ScholarPubMed
7. Tune, L, Gucker, S, Folstein, M, et al. Cerebrospinal fluid acetylcholinesterase activity in senile dementia of the Alzheimer type. Ann Neurol 1985; 17: 4648.Google Scholar
8. Nakano, S, Kato, T, Nakamura, S, et al. Acetylcholinesterase activity in cerebrospinal fluid of patients with Alzheimer’s disease and senile dementia. J Neurol Sci 1986; 75: 213223.Google Scholar
9. Atack, JR, May, C, Kaye, JA, et al. Cerebrospinal fluid cholinesteras- es in aging and in dementia of the Alzheimer type. Ann Neurol 1988; 23: 161167.CrossRefGoogle Scholar
10. Sirvio, J, Kutvonen, R, Soininen, H, et al. Cholinesterases in the cerebrospinal fluid, plasma, and erythrocytes of patients with Alzheimer’s disease. J Neural Transm 1989; 75: 119127.CrossRefGoogle ScholarPubMed
11. Davies, P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res, Amsterdam 1979; 171: 319327.CrossRefGoogle ScholarPubMed
12. Deutsch, SI, Mohs, RC, Levy, MI, et al. Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer’s disease and normals. Biol Psychiatry 1983; 18: 13531373.Google Scholar
13. Lal, S, Wood, PL, Kiely, ME, et al. CSF acetylcholinesterase in dementia and in sequential samples of lumbar CSF. Neurobiol Aging 1984; 5: 269274.Google Scholar
14. Marquis, JK, Volicer, L, Mark, KA, et al. Cholinesterase activity in plasma, erythrocytes and cerebrospinal fluid of patients with dementia of the Alzheimer type. Biol Psychiatry 1985; 20: 605610.Google Scholar
15. Huff, FJ, Maire, J-C, Growdon, JH, et al. Cholinesterases in cerebrospinal fluid: Correlations with clinical measures in Alzheimer’s disease. J Neurol Sci 1986; 72: 121129.Google Scholar
16. Ruberg, M, Villageois, A, Bonnet, A-M, et al. Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems. J Neurol Neurosurg Psychiatry 1987; 50: 538543.Google Scholar
17. Elble, R, Giacobini, E, Scarsella, GF. Cholinesterases in cerebrospinal fluid: A longitudinal study in Alzheimer disease. Arch Neurol 1987; 44: 403407.CrossRefGoogle ScholarPubMed
18. Appleyard, ME, Smith, AD, Berman, P, et al. Cholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Brain 1987; 110: 13091322.CrossRefGoogle ScholarPubMed
19. Augustinsson, K-B, Bartfai, T, Mannervik, B. A steady-state kinetic model of butyrylcholinesterase from horse plasma. Biochem J 1974; 141: 825834.CrossRefGoogle ScholarPubMed
20. McKhann, G, Drachman, D, Folstein, M, et al. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34: 939944.CrossRefGoogle ScholarPubMed
21. Hachinski, VC, Iliff, LD, Zilhka, E, et al. Cerebral blood flow in dementia. Arch Neurol 1975; 32: 632637.Google Scholar
22. Mattis, S. Mental status examination for organic mental syndrome in the elderly patient. In: Geriatric Psychiatry. Edited by Bellack, R. and Karasu, B.. New York: Grune and Stratton 1976; 77121.Google Scholar
23. Vitaliano, PP, Breen, AR, Russo, J, et al. The clinical utility of the Dementia Rating Scale for assessing Alzheimer patients. J Chronic Dis 1984; 37: 743753.Google Scholar
24. Steele, MW, Wenger, SL, Chorazy, A, et al. Chromosome site of 4q21 and Huntington-like disease. Am J Hum Genet 1987; 41: A85.Google Scholar
25. Johnson, CD, Russell, RL. A rapid, simple radiometric assay for cholinesterase, suitable for multiple determinations. Anal Biochem 1975; 64: 229238.CrossRefGoogle ScholarPubMed
26. Huff, FJ, Reiter, CT, Rand, JB. The ratio of acetylcholinesterase to butyrylcholinesterase influences the specificity of assays for each enzyme in human brain. J Neural Transm 1989; 75: 129134.Google Scholar
27. Bisso, GM, Masullo, C, Michalek, H, et al. Molecular forms of cholinesterases in CSF of Alzheimer’s disease/senile dementia of Alzheimer type patients and matched neurological controls. Life Sci 1986; 38: 561567.Google Scholar
28. Perry, EK, Perry, RH. Brain biochemistry in dementia of Alzheimer-type. In: Metabolic Disorders of the Nervous System. Edited by Rose, F.C.. London: Pitman 1981; 382417.Google Scholar