Summary
Several neurotransmitter markers were investigated in the cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) (n=27), Parkinson's disease (PD) (n=35) and ALS (n=26) and from control subjects (n=34) to compare the possible alterations in the biochemical profiles of these different neurodegenerative diseases. The main proportion of the patients represented an early phase of the illness at the time of the diagnosis. Correlations of the degree of dementia and the stage of the disease with CSF measures were evaluated. The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly reduced in AD patients when compared with those of normals and ALS patients. The CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD patients and the decrease focused on the nondemented patients. A trend of decreasing HVA values towards the most advanced stage of Parkinson's disease assessed by Webster's scale was also displayed. The content of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in the PD group and the lowest acetylcholinesterase (AChE) activities were found in the PD patients with the most severe disease. Changes in CSF measures were too subtle to be beneficial for diagnostic purposes, but adequate for reflecting the different neurochemical profiles of these three degenerative neurological disorders.
Similar content being viewed by others
References
Appleyard ME, Smith AD, Wilcock GK, Esiri MM (1983) Decreased CSF acetylcholinesterase activity in Alzheimer's disease. Lancet ii: 452
Arendt T, Bigl V, Walther F, Sonntag M (1984) Decreased ratio of CSF acetylcholinesterase to butyrylcholinesterase activity in Alzheimer's disease. Lancet i: 173
Atack JR, Beal MF, Kaye JA, Mazurek MF, Kay AD, Rapoport SI (1988a) Cerebrospinal fluid somatostatin and neuropeptide Y, concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs. Arch Neurol 45: 269–274
Atack JR, May C, Kaye JA, Kay AD, Rapoport SI (1988b) Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type. Ann Neurol 23: 161–167
Bareggi SR, Franceschi M, Bonini L, Zecca L, Smirne S (1982) Decreased CSF concentration of homovanillic acid and gamma-aminobutyric acid in Alzheimer's disease. Arch Neurol 39: 709–712
Beal MF, Growdon JH, Mazurek MF, Martin JB (1986) CSF Somatostatin-like immunoreactivity in dementia. Neurology 36: 294–297
Bisso GM, Massullo C, Michalek H, Silveri MC, Pocchiari M (1986) Molecular forms of cholinesterases in CSF of Alzheimer's disease/senile dementia of Alzheimer type patients and age matched neurological controls. Life Sci 38: 561–567
Davies P (1979) Neurotransmitter-related enzymes in senile dementia of Alzheimer type. Brain Res 171: 319–327
Deutsch SI, Mohs RC, Levy MI, Rothpearl AB, Stocton B, Hovarth T, Coco A, Davies KL (1983) Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer's disease and normals. Biol Psychiatry 18: 1363–1373
Direnfeld LK, Albert ML, Volicer L, Laglais PJ, Marquis J, Kaplan E (1984) Parkinson's disease. The possible relationship of laterality to dementia and neurochemical findings. Arch Neurol 41: 935–941
Dubois B, Danze F, Pillon B, Cusimano G, Lhermitte F, Agid Y (1987) Cholinergic dependent cognitive deficits in Parkinson's disease. Ann Neurol 22: 26–30
Dupont E, Christensen SE, Hansen AP, Olivarius BF, Orskov H (1982) Low cerebrospinal fluid somatostatin in Parkinson disease: an irreversible abnormality. Neurology 32: 312–314
Ehringer H, Hornykiewicz O (1960) Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Wien Klin Wschr 38: 1236–1239
Elble R, Giacobini E, Scarsella GF (1987) Cholinesterases in cerebrospinal fluid. A longitudinal study in Alzheimer's disease. Arch Neurol 44: 403–407
Elovaara I, Icen, A, Palo J, Erkinjuntti T (1985) CSF in Alzheimer's disease. Studies on blood-brain barrier function and intrathecal protein synthesis. J Neurol Sci 70: 73–80
Facchinetti F, Nappi G, Petraglia F, Martignoni E, Sinforiani, E, Genazzani AR (1984) Central ACTH deficit in degenerative and vascular dementia. Life Sci 35: 1691–1697
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 Parkinson's syndrome. J Neurochem 16: 1341–1344
Hartikainen P, Soininen H, Reinikainen KJ, Sirviö J, Soikkeli R, Riekkinen P (1991) Neurotransmitter markers in the CSF of normal subjects. Effects of aging and other confounding factors. J Neural Transm [Gen Sect] 84: 103–117
Hornykiewicz O (1966) Dopamine and brain function. Pharmacol Rev 18: 925–964
Hoehn MM, Yahr MD (1967) Parkinsonism — onset, progression and mortality. Neurology 17: 427–442
Huff FJ, Maire JL, Growdon JH, Corkin S, Wurtman R (1986) Cholinesterases in cerebrospinal fluid; correlations with clinical measures in Alzheimer's disease. J Neurol Sci 72: 121–129
Hughes CP, Berg L, Danzinger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140: 566–572
Hurst JH, LeWitt PA, Burns RS, Foster NL, Lovenberg W (1985) CSF dopamine-β-hydroxylase activity in Parkinson's disease. Neurology 35: 565–568
Johansson B, Roos B (1967) 5-Hydroxyindoleacetic and homovanillic acid levels in the cerebrospinal fluid of healthy volunteers and patients with Parkinson's syndrome. Life Sci 6: 1149–1154
Johnson S, Domino EF (1971) Cholinergic enzymatic activity of cerebrospinal fluid of patients with various neurological disease. Clin Chim Acta 35: 421–428
Jolkkonen J, Soininen H, Halonen T, Ylinen A, Laulumaa V, Laakso M, Riekkinen P (1986) Somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with Parkinson's disease and its relation to dementia. J Neurol Neurosurg Psychiatry 49: 1374–1377
Jolkkonen J, Lehtinen M, Soininen H, Sennef C, Riekkinen P (1987a) Enhanced monoaminergic neurotransmission by desglycinamide-arginine-vasopressin in human subjects. Neurosci Lett 76: 312–315
Jolkkonen JT, Soininen HS, Riekkinen PJ (1987b) β-Endorphin-like immunoreactivity in cerebrospinal fluid of patients with Alzheimer's disease and Parkinson's disease. J Neurol Sci 77: 153–159
Jolkkonen J, Soikkeli R, Hartikainen P, Bissette G, Riekkinen P (1990) CSF neuropeptides in Alzheimer's disease and Parkinson's disease. Anuario Psiquiatrico 1: 251–257
Jonker C, Eikelenboom P, Tavenier P (1982) Immunological indices in the cerebrospinal fluid of patients with presenile dementia of the Alzheimer type. Br J Psychiatry 140: 44–49
Kaiya H, Tanaka T, Takeuchi K, Adachi S, Shirakawa H, Yeki H, Namba M (1983) Decreased levels of β-endorphin-like immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Life Sci 33: 1039–1043
Kay AD, Milstien S, Kaufman S, Creasey H, Haxby JV, Cutler NR, Rapoport SI (1986) Cerebrospinal fluid biopterin is decresed in Alzheimer's disease. Arch Neurol 43: 996–999
Kaye JA, May C, Daly E, Atack JR, Sweeney DJ, Luxenburg JS, Kay AD, Kaufman S, Milstien S, Friedland RP, Rapoport SI (1988a) Cerebrospinal fluid monoamine markers are decreased in dementia of the Alzheimer type with extrapyramidal features. Neurology 38: 554–557
Kaye JA, May C, Atack JR, Daly E, Sweeney DL, Beal MF, Kaufman S, Milstien S, Friedland RP, Rapoport SI (1988b) Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease. Ann Neurol 24: 647–650
Kostic VS, Djuricic BM, Covickovic-Sternic N, Bumbasirevic L, Nikolic M, Mrsulja BB (1987) Depression and Parkinson's disease: possible role of serotonergic mechanisms. J Neurol 234: 94–96
Koyama E, Minegishi A, Ishizaki T (1988) Simultaneous determination of four monoamine metabolites and serotonin in cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection; application for patients with Alzheimer's disease. Clin Chem 34: 680–684
Kumar V, Giacobini E, Markwell S (1989) CSF choline and acetylcholinesterase in earlyonset vs. late-onset Alzheimer's disease patients. Acta Neurol Scand 80: 461–466
Lal S, Wood PL, Kiely ME, Etienne P, Gauthier S, Stradford J, Ford RM, Dastoor D, Nair NPV (1984) CSF acetylcholinesterase in dementia and in sequential samples of lumbar CSF. Neurobiol Aging 5: 269–274
Lowry OH, Rosenbrough NJ, Farr AL, Randall RS (1951) Protein measurement with the Folin phenol method. J Biol Chem 193: 265–275
Mann JJ, Stanley M, Neophytides A, de Leon MJ, Ferris SH, Gershon S (1981) Central amine metabolism in Alzheimer's disease: in vivo relationship to cognitive deficit. Neurobiol Aging 2: 57–60
Manyam BV, Giacobini E, Colliver JA (1990) Cerebrospinal fluid choline levels are decreased in Parkinson's disease. Ann Neurol 27: 683–685
May C, Rapoport SI, Tomai TP, Chrousos GP, Gold PW (1987) Cerebrospinal fluid concentrations of corticotropin releasing hormone (CRH) and corticotropin (ACTH) are reduced in patients with Alzheimer's disease. Neurology 37: 535–538
May C, Kaye JA, Atack JR, Schapiro MB, Friedland RP, Rapoport SI (1990) Cerebrospinal fluid production is reduced in healthy aging. Neurology 40: 500–503
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease; a report of NINCDS-ADRDA Work group under auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 34: 939–944
Miyata S, Nagata H, Yamao S, Nakamura S, Kameyama M (1984) Dopamine-β-hydroxylase activities in serum and cerebrospinal fluid of aged and demented patients. J Neurol Sci 63: 403–409
Nagatsu T, Wakui Y, Kato T, Fujita K, Kondo T, Yokochi F, Narabayashi H (1982) Dopamine-β-hydroxylase activity in cerebrospinal fluid of parkinsonian patients. Biomed Res 3: 95–98
Nakano S, Kato T, Nakamura S, Kameyama M (1986) Acetylcholinesterase activity in cerebrospinal fluid of patients with Alzheimer's disease and senile dementia. J Neurol Sci 75: 213–223
Nappi G, Petraglia F, Martignoni E, Facchinetti F, Bono G, Genazzani AR (1985) β-Endorphin cerebrospinal fluid decrease in untreated parkinsonian patients. Neurology 35: 1371–1374
Nappi G, Facchinetti F, Martignoni E, Petraglia F, Sinforiani E, Bono G, Genazzani AR (1988) N-terminal ACTH fragments increase the CSF β-EP content in Alzheimer type dementia. Acta Neurol Scand 78: 146–151
Palmer AM, Sims NR, Bowen DM, Neary D, Palo J, Wikström J, Davison AN (1984) Monoamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia. J Neurol Neurosurg Psychiatry 47: 481–484
Palmer AM, Wilcock GK, Esiri MM, Francis PT, Bowen DM (1987) Monoaminergic innervation of the frontal and temporal lobes in Alzheimer's disease. Brain Res 401: 231–238
Parkes JD, Marsden CD, Rees JE, Gurzon G, Kantameni BD, Knill-Jones R, Akbar A, Das S, Kataria M (1974) Parkinson's disease, cerebral arteriosclerosis, and senile dementia. Clinical features and response to levodopa. Q J Med 169: 49–61
Perry EK (1986) The cholinergic hypothesis — ten years on. Br Med Bull 42: 63–69
Raskind MA, Peskind ER, Halter JB, Jimerson DC (1984) Norepinephrine and MHPG levels in CSF and plasma in Alzheimer's disease. Arch Gen Psychiatry 41: 343–346
Reinikainen KJ, Riekkinen PJ, Jolkkonen J, Kosma V-M, Soininen H (1987) Decreased somatostatin-like immunoreactivity in cerebral cortex and cerebrospinal fluid in Alzheimer's disease. Brain Res 402: 103–108
Reinikainen KJ, Riekkinen PJ, Paljärvi L, Soininen H, Helkala E-L, Jolkkonen J, Laakso M (1988a) Cholinergic deficit in Alzheimer's disease: a study based on CSF and autopsy data. Neurochem Res 13: 135–146
Reinikainen KJ, Paljärvi L, Halonen T, Malminen O, Kosma V-M, Laakso M, Riekkinen PJ (1988b) Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease. Neurobiol Aging 9: 245–252
Reinikainen KJ, Riekkinen PJ (1990) Noncholinergic neurotransmitter markers in the CSF of patients with dementia of Alzheimer type. In: Fowler CJ, Carlson LA, Gottfries CG, Winblad B (eds) Biological markers in dementia of Alzheimer type. Aging and aging disorders, vol 1. Smith-Gordon Nishimura, London, pp. 161–178
Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A (1980) Pathological verfication of ishaemic score in differentiation of dementias. Ann Neurol 7: 486–488
Rossor MN, Garret NJ, Johnson AL, Mountjoy CQ, Roth M, Iversen LL (1982) A postmortem study of the cholinergic and GABA systems in senile dementia. Brain 105: 313–330
Ruberg M, Villageois A, Bonnet AM, Pillon B, Rieger F, Agid Y (1987) Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems. J Neurol Neurosurg Psychiatry 50: 538–543
Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease. Brain Res 275: 321–328
Siegel S, Castellan NJ (1988) Nonparametric statistics for the behavioral sciences, 2nd edn. McGraw-Hill, Singapore, pp 213–215
Sirviö J, Soininen HS, Kutvonen R, Hyttinen J-M, Helkala E-L, Riekkinen PJ (1987) Acetyl- and butyrylcholinesterase activity in the cerebrospinal fluid of patients with Parkinson's disease. J Neurol Sci 63: 167–172
Sirviö J, Kutvonen R, Hartikainen P, Riekkinen PJ (1989a) Cholinesterases in the cerebrospinal fluid, plasma, and erythrocytes of patients with Alzheimer's disease. J Neural Transm 75: 119–27
Sirviö J, Rinne JO, Valjakka A, Rinne UK, Riekkinen PJ, Paljärvi L (1989b) Different forms of brain acetylcholinesterase and muscarinic binding in Parkinson's disease. J Neurol Sci 90: 23–32
Soininen H, Halonen T, Riekkinen PJ (1981a) Acetylcholinesterase activities in cerebrospinal fluid of patients with senile dementia of the Alzheimer type. Acta Neurol Scand 64: 217–224
Soininen H, Mc Donald E, Rekonen M, Riekkinen PJ (1981b) Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Acta Neurol Scand 64: 101–107
Soininen H, Pitkänen A, Halonen T, Riekkinen PJ (1984a) Dopamine-β-hydroxylase and acetylcholinesterase activities in cerebrospinal fluid in Alzheimer's disease. Acta Neurol Scand 69: 29–34
Soininen HS, Jolkkonen J, Reinikainen KJ, Halonen TO, Riekkinen PJ (1984b) Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of Alzheimer type. J Neurol Sci 63: 167–172
Sulkava R, Erkinjuntti T, Laatikainen T (1985) CSF β-endorphin and β-lipotropin in Alzheimer's disease and multi-infarct dementia. Neurology 35: 1057–1058
Tune L, Gucker S, Folstein M, Oshida L, Coyle JT (1985) Cerebrospinal fluid acetylcholinesterase activity in senile dementia of the Alzheimer type. Ann Neurol 17: 46–48
Turkka JT, Juujärvi KK, Myllylä VV (1987) Correlation of autonomic dysfunction to CSF concentrations of noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's disease. Eur Neurol 26: 29–34
Urakami K, Adachi Y, Awaki E, Takahashi K (1989) Characterization of the course of senile dementia of the Alzheimer type using cerebrospinal fluid levels of acetylcholinesterase and somatostatin. Acta Neurol Scand 80: 232–237
Volicer L, Langlais PJ, Mattson WR, Mark KA, Gamache PH (1985) Serotonergic system in dementia of the Alzheimer type; abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid. Arch Neurol 42: 1158–1161
Webster DD (1986) Clinical analysis of the disability on Parkinson's disease. Mod Treat 5: 257–262
Webster P, Eriksson S, Forsell Å, Puu G, Adolfsson R (1988) Monoamine metabolite concentrations and cholinesterase activities in cerebrospinal fluid of progressive dementia patients: relation to clinical parameters. Acta Neurol Scand 77: 12–21
Wood PL, Etienne P, Lal S, Gauthier S, Cajal S, Nair NPV (1982) Reduced lumbar CSF somatostatin levels in Alzheimer's disease. Life Sci 31: 2073–2079
Zubenko GS, Marquis JK, Volicer L, Direnfeld LK, Langlais PJ, Nixon RA (1986) Cerebrospinal fluid levels of angiotensinconverting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study. Biol Psychiatry 21: 1365–1381
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hartikainen, P., Reinikainen, K.J., Soininen, H. et al. Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls. J Neural Transm Gen Sect 4, 53–68 (1992). https://doi.org/10.1007/BF02257622
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02257622