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Increased CSF HVA response to arecoline challenge in Alzheimer's disease

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Summary

The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p<.01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.

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References

  • Anden NE (1974) Effects of oxotremorine and physostigmine on the turnover of dopamine in the corpus striatum and the limbic system. J Pharm Pharmacol 26: 738–740

    Google Scholar 

  • Araujo DM, Lapchak PA, Robitaille Y, Gauthier S, 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

    Google Scholar 

  • Aubert I, Cecyre D, Araujo DM, Gauthier S, Quirion R (1990) Alterations of the cholinergic system in Alzheimer's and Parkinson's diseases. Neurobiology of Aging: The second International Conference on Alzheimer's Disease and Related Disorders 11: 340 (Abstract)

    Google Scholar 

  • Bareggi SR, Franceschi M, Bonini L, Zecca L, Smirne S (1982) Decreased CSF concentrations of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease: age- or disease-related modifications? Arch Neurol 39: 709–712

    Google Scholar 

  • Bartholini G, Keller HH, Pletscher A (1975) Drug induced changes of dopamine turnover in striatum and limbic system of the rat. J Pharm Pharmacol 27: 439–442

    Google Scholar 

  • Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417

    Google Scholar 

  • Bhatnager SP (1973) Studies related to the cholinergic influence on the accumulation and disappearance of monamines in the rat brain. Can J Neurol Sci 51: 893–899

    Google Scholar 

  • Bowen DM, Smith CB, White P, Flack RHA, Carrasco LH, Gedye JL, Davison AN (1977) Chemical pathology of organic dementia. Brain 100: 427–453

    Google Scholar 

  • Bowen DM, Allen SJ, Benton JS, Goodhardt MJ, Haan EA, Palmer AM, Sims NR, Smith CCT, Spillane JA, Esiri MM, Neary D, Snowden JS, Wilcock GK, Davison AN (1983) Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J Neurochem 41: 266–272

    Google Scholar 

  • Caulfield MP, Sraughan DW, Cross AJ, Crow T, Birdsall NJM (1982) Cortical muscarinic receptor subtypes and Alzheimer's disease. Lancet ii: 1277

    Google Scholar 

  • Corrodi H, Fuxe K, Hammer W, Sjogvist F, Ungerstedt U (1967) Oxotremorine and central monamine neurones. Life Sci 6: 2557–2566

    Google Scholar 

  • Dam M, Wamsley JK, Rapoport SL, London ED (1982) Effects of oxotremorine on local glucose utilization in the rat cerebral cortex. J Neurosci 2: 1072–1078

    Google Scholar 

  • Danielsson E, Eckernas SA, Danielsson AW, Nordstrom O, Bartfai T, Gottfries CG, Wallin A (1988) VIP sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer's disease/senile dementia of the Alzheimer type. Neurobiol Aging 9: 153–162

    Google Scholar 

  • Davidson DLW, Yates CM, Mawdsley C, Pular IA, Wilson H (1977) CSF studies on the relationship between dopamine and 5-hydroxytryptamine in Parkinsonism and other movement disorders. J Neurol Neurosurg Psychiatry 40: 1136–1141

    Google Scholar 

  • Davies P, Maloney AJF (1976) Selective loss of central cholinergic neurons in Alzheimer's disease (Letter to the Editor). Lancet ii: 1403

    Google Scholar 

  • Davies P, Verth A (1978) Regional distribution of muscarinic acetylcholine receptor in normal and Alzheimer's type dementia brains. Brain Res 138: 385–392

    Google Scholar 

  • Davis KL, Hollister LE, Goodwin FK, Gordon EK (1977) Neurotransmitter metabolites in the cerebrospinal fluid of man following physostigmine. Life Sci 21: 933–936

    Google Scholar 

  • Davis KL, Faull KF, Hollister LE, Barchas JD, Berger PA (1981) Alterations in cerebrospinal fluid dopamine metabolites following physostigmine infusion. Psychopharmacology 72: 155–160

    Google Scholar 

  • Davis KL, Thal L, Gamzu E, Gracon S, THA Collaborative Study Group (1989) THA: report of work in progress. American College of Neuropsychopharmacology 28th Annual Meeting, December 10–15, Maui, Hawaii (Abstract)

  • DeKosky ST, Scheff SW, Markesbery WR (1985) Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer's disease and aging. Neurology 35: 1425–1431

    Google Scholar 

  • Drachman DA (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27: 783–790

    Google Scholar 

  • Elsworth JD, Leahy DJ, Roth RH, Redmond DE (1987) Homovanillic acid concentration in brain, CSF and plasma as indicators of central dopamine function in primates. J Neural Transm 68: 51–62

    Google Scholar 

  • Gottfries CG, Roos BE (1973) Acid monoamine metabolites in cerebrospinal fluid from patients with presenile dementia (Alzheimer's disease). Acta Psychiatr Scand 49: 257–263

    Google Scholar 

  • Gottfries CG, Gottfries I, Roos BE (1969) Homovanillic acid and 5 hydroxyindoleacetic acid in the cerebrospinal fluid of patients with senile dementia, presenile dementia and Parkinsonism. J Neurochem 16: 1341–1345

    Google Scholar 

  • Gottfries CG, Gottfries I, Roos BE (1969) The investigation of homovanillic acid in human in brain and its correlation to senile dementia. Br J Psychiatry 115: 563–574

    Google Scholar 

  • Harrison PJ, Barton AJL, Najlerahim A, McDonald B, Pearson RCA (1991) Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry. Mol Brain Res 9: 15–21

    Google Scholar 

  • Inzelberg R, Shapira T, Korczyn AD (1990) Effects of atropine on learning and memory functions in dementia. Clin Neuropharmacol 13: 241–247

    Google Scholar 

  • Javoy F, Agid Y, Bouvet D, Glowinski J (1974) Changes on neostriatal DA metabolism after carbachol or atropine microinjections in the substantia nigra. Brain Res 68: 253

    Google Scholar 

  • Jenni-Eiermann S, von Hahn HP, Honegger CG, Ulrich J (1984) Studies on neurotransmitter binding in senile dementia: comparison of Alzheimer's and mixed vascular-Alzheimer's dementias. Gerontology 30: 350–358

    Google Scholar 

  • Kellar KJ, Whitehouse PJ, Martino-Barrows AM, Marcus K, Price DL (1987) Muscarinic and nicotinic cholinergic binding sites in Alzheimer's disease cerebral cortex. Brain Res 436: 62–68

    Google Scholar 

  • Knott P, Haroutunian V, Bierer L, Perl D, Handler M, DeLeon M, Yang RK, Davis K (1989) Correlations post-mortem between ventricular CSF and cortical tissue concentrations of MHPG, 5-HIAA and HVA in Alzheimer's disease. Biol Psychiatry 25: 111A-119A

    Google Scholar 

  • 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: 271–280

    Google Scholar 

  • Lerer B (1985) Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium. Biol Psychiatry 20: 20–40

    Google Scholar 

  • Lerer B, Stanley M, Demetriou S, Gershorn S (1983) Effect of electroconvulsive shock on muscarinic cholinergic receptors in rat cerebral cortex and hippocampus. J Neurochem 41: 1680–1683

    Google Scholar 

  • Lippa AS, Bartus R (1982) Neurobiological aspects of geriatric cognitive dysfunction. In: Corkin S, Davis KL, Growdon JH, Wurtman RJ (eds) Alzheimer's disease: a report of progress in research. Raven Press, New York, pp 223–233 (Aging, vol 19)

    Google Scholar 

  • Mann DMA, Yates PO, Marcyniuk B (1987) Dopaminergic neurotransmitter systems in Alzheimer's disease and in Down's syndrome at middle age. J Neurol Neurosurg Psychiatry 50: 341–344

    Google Scholar 

  • Marks MJ, O'Connor MF, Artman LD, Burch JB, Collins AC (1984) Chronic scopolamine treatment and brain cholinergic function. Pharmacol Biochem Behav 20: 771–777

    Google Scholar 

  • Mash DC, Flynn DD, Potter LT (1985) Loss of M 2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 228: 1115–1117

    Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) 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 34: 939–944

    Google Scholar 

  • Molinengo L, Cassone MC, Orsetti M (1986) Action of arecoline on the levels of acetylcholine, norepinephrine and dopamine in the mouse central nervous system. Pharmacol Biochem Behav 24: 1801–1803

    Google Scholar 

  • Murphy MF (1989) HP 029: a new anticholinesterase for Alzheimer's disease. American College of Neuropsychopharmacology, 28 th Annual Meeting, December 10–15, Maui, Hawai (Abstract)

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

    Google Scholar 

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

    Google Scholar 

  • Palacios JM (1982) Autoradiographic localization of muscarinic cholinergic receptors in the hippocampus of patients with senile dementia. Brain Res 243: 173–175

    Google Scholar 

  • Palmer AM, Sims NR, Bowen DM, Neary D, Palo J, Wikstrom J, Davison AN (1984) Monamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia. J Neurol Neurosurg Psychiatry 47: 481–484

    Google Scholar 

  • Parnetti L, Gottfries J, Karlsson I, Langstrom G, Gottfries CG, Svennerholm (1987) Monamines and their metabolites in cerebrospinal fluid of patients with senile dementia of Alzheimer type using high performance liquid chromatography and gas chromatography-mass spectrometry. Acta Psychiatr Scand 75: 542–548

    Google Scholar 

  • Pedigo NW, Minor LD, Krumrei TN (1984) Cholinergic drug effects and brain muscarinic receptor binding in aged rats. Neurobiol Aging 5: 227–233

    Google Scholar 

  • Perry EK, Perry RH, Blessed G, Tomlinson BE (1977) Necropsy evidence of central cholinergic deficits in senile dementia (Letter to the editor). Lancet ii: 189

    Google Scholar 

  • Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2: 1457–1459

    Google Scholar 

  • Pletscher A, Bartholini G, Tissot R (1967) Metabolic fate of L-[14C] DOPA in cerebrospinal fluid and blood plasma of humans. Brain Res 4: 106–109

    Google Scholar 

  • Pomara N, Stanley M (1986) The functional status of central muscarinic receptors in Alzheimer's disease: assessment and therapeutic implications. In: Crook T, Bartus R, Ferris S, Gershon S (eds) Treatment development strategies for Alzheimer's disease. Mark Powley Associates, New Canaan CT, pp 451–472

    Google Scholar 

  • Post RM, Allen FH, Ommaya AK (1974) Cerebrospinal fluid flow and iodide transport in the spinal subarachnoid space. Life Sci 14: 1885–1894

    Google Scholar 

  • Quirion R, Martel JC, Robitaille Y, Etienne P, Wood P, Nair NPV, Gauthier S (1986) Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type. Can J Neurol Sci 13: 503–510

    Google Scholar 

  • Reinikainen KJ, Riekkinen PJ, Halonen T, Laakso M (1987) Decreased muscarinic receptor binding in cerebral cortex and hippocampus in Alzheimer's disease. Life Sci 41: 453–461

    Google Scholar 

  • Reisberg B, Ferris SH, de Leon MJ, Crook T (1982) The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 139: 1136–1139

    Google Scholar 

  • Reisine TD, Yamamura HI, Bird ED, Spokes E, Enna SJ (1978) Pre- and postsynaptic neurochemical alterations in Alzheimer's disease. Brain Res 159: 477–481

    Google Scholar 

  • Riehl JL, Paul-David J, Unnak R (1962) Comparison of the effects of arecoline and muscarine on the central nervous system. Int J Neuropharmacol 1: 393

    Google Scholar 

  • Rinne JO, Rinne JK, Laakso K, Paljarvi L, Rinne UK (1984) Reduction in muscarinic receptor binding in limbic areas of Alzheimer brain. J Neurol Neurosurg Psychiatry 47: 651–652

    Google Scholar 

  • Rinne JO, Laakso K, Lonnberg P, Molsa P, Paljarvi L, Rinne JK, Sako E, Rinne UK (1985) Brain muscarinic receptors in senile dementia. Brain Res 336: 19–25

    Google Scholar 

  • Rossor NM (1982) Neurotransmitters and CNS disease: dementia. Lancet ii: 1200–1204

    Google Scholar 

  • Sachs DI, Kloog Y, Korczyn AD, Heron DS, Sokolovsky M (1979) Denervation, supersensitivity and muscarinic receptors in the cat iris. Clin Pharm 28: 1513–1518

    Google Scholar 

  • Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DI, Davison AN (1983) Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40: 503–509

    Google Scholar 

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

    Google Scholar 

  • Soininen H, MacDonald E, Rekonen M, Riekkinen PJ (1981) Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Acta Neurol Scand 64: 101–107

    Google Scholar 

  • Soncrant TT, Nurnberger J (1989) Measuring cholinergic sensitivity. II. Arecoline effects on metabolic activity in pontine regions of rat brain. Biol Psychiatry 25: 618–625

    Google Scholar 

  • Stanley M, Traskman-Bendz L, Dorovini-Zis K (1985) Correlations between aminergic metabolities simultaneously obtained from human CSF and brain. Life Sci 37: 1279–1286

    Google Scholar 

  • Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA, Murphy DL (1987) Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age matched controls. A dose-response study. Arch Gen Psychiatry 44: 418–426

    Google Scholar 

  • Tariot PN, Cohen RM, Welkowitz JA, Sunderland T, Newhouse PA, Murphy DL, Weingartner H (1988) Multiple-dose arecoline infusions in Alzheimer's disease. Arch Gen Psychiatry 45: 901–905

    Google Scholar 

  • Ulus RH, Wurtman RJ (1976) Choline adminstration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain. Science 194: 1060–1061

    Google Scholar 

  • Westerink BHC, Korf J (1975) Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain. Eur J Pharmacol 33: 31–40

    Google Scholar 

  • White P, Goodhardt MJ, Keet JP, Hiley CR, Carrasco LH, Williams IEI, Bowen DM (1977) Neocortical cholinergic neurons in elderly people. Lancet i: 668–671

    Google Scholar 

  • Whitehouse PJ, Kellar KJ (1987) Nicotinic and muscarinic cholinergic receptors in Alzheimer's disease and related disorders. J Neural Transm [Suppl] 24: 175–182

    Google Scholar 

  • 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: 1237–1239

    Google Scholar 

  • Wood PL, Etienne P, Lal S, Nair NPV, Finlayson MH, Gauthier S, Palo J, Haltia M, Paetau A, Bird ED (1983) A post-mortem comparison of the cortical cholinergic system in Alzheimer's disease and Pick's disease. J Neurol Sci 62: 211–217

    Google Scholar 

  • Yates CM, Allison Y, Simpson J, Maloney AFJ, Gordon A (1979) Dopamine in Alzheimer's disease and senile dementia (Letter to the editor). Lancet: 851–852

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Pomara, N., Stanley, M., LeWitt, P.A. et al. Increased CSF HVA response to arecoline challenge in Alzheimer's disease. J. Neural Transmission 90, 53–65 (1992). https://doi.org/10.1007/BF01250518

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