Journal Mobile Options
Table of Contents
Vol. 21, No. 1, 2006
Issue release date: December 2005
Dement Geriatr Cogn Disord 2006;21:9–15
(DOI:10.1159/000089137)

Measurement of Thirteen Biological Markers in CSF of Patients with Alzheimer’s Disease and Other Dementias

Blasko I. · Lederer W. · Oberbauer H. · Walch T. · Kemmler G. · Hinterhuber H. · Marksteiner J. · Humpel C.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer’s disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using β-amyloid 1–42 (Aβ42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Aβ42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-α, TGF-β1, MIP-1α) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Aβ42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Aβ42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2003;2:605–613.
  2. Hampel H, Buerger K, Zinkowski R, Teipel SJ, Goernitz A, Andreasen N, Sjoegren M, DeBernardis J, Kerkman D, Ishiguro K, Ohno H, Vanmechelen E, Vanderstichele H, McCulloch C, Moller HJ, Davies P, Blennow K: Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Arch Gen Psychiatry 2004;61:95–102.
  3. Maddalena A, Papassotiropoulos A, Muller-Tillmanns B, Jung HH, Hegi T, Nitsch RM, Hock C: Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol 2003;60:1202–1206.
  4. Hock C, Heese K, Muller-Spahn F, Huber P, Riesen W, Nitsch RM, Otten U: Increased CSF levels of nerve growth factor in patients with Alzheimer’s disease. Neurology 2000;54:2009–2011.
  5. Sun YX, Minthon L, Wallmark A, Warkentin S, Blennow K, Janciauskiene S: Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 2003;16:136–144.
  6. Galimberti D, Schoonenboom N, Scarpini E, Scheltens P: Chemokines in serum and cerebrospinal fluid of Alzheimer’s disease patients. Ann Neurol 2003;53:547–548.
  7. Tarkowski E, Liljeroth AM, Nilsson A, Ricksten A, Davidsson P, Minthon L, Blennow K: TNF gene polymorphism and its relation to intracerebral production of TNFalpha and TNFbeta in AD. Neurology 2000;54:2077–81.
  8. Tarkowski E, Issa R, Sjogren M, Wallin A, Blennow K, Tarkowski A, Kumar P: Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer’s disease and vascular dementia. Neurobiol Aging 2002;23:237–243.
  9. Stopa EG, Berzin TM, Kim S, Song P, Kuo-LeBlanc V, Rodriguez-Wolf M, Baird A, Johanson CE: Human choroid plexus growth factors: what are the implications for CSF dynamics in Alzheimer’s disease? Exp Neurol 2001;167:40–47.
  10. Grundstrom E, Lindholm D, Johansson A, Blennow K, Askmark H: GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis. Neuroreport 2000;11:1781–1783.
  11. Chiaretti A, Piastra M, Polidori G, Di Rocco C, Caresta E, Antonelli A, Amendola T, Aloe L: Correlation between neurotrophic factor expression and outcome of children with severe traumatic brain injury. Intensive Care Med 2003;29:1329–1338.
  12. Murray KD, Gall CM, Jones EG, Isackson PJ: Differential regulation of brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer’s disease. Neuroscience 1994;60:37–48.
  13. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology 1989;39:1159–1165.
  14. Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry 1994;57:416–418.
  15. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: 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;34:939–944.
  16. Dilling H, Mombour W, Schmidt MH: ICD-10 – International Classification of Psychiatric Diseases. Berne, Leck, Huber, Clausen & Bosse, 1997, chapter V.
  17. Folstein MF, Robins LN, Helzer JE: The Mini-Mental State Examination. Arch Gen Psychiatry 1983;40:812.
  18. Nauck M, Hoffmann MM, Wieland H, Marz W: Evaluation of the apoE genotyping kit on the Light Cycler. Clin Chem 2000;46:722–724.
  19. Metz CE: Basic principles of ROC analysis. Semin Nucl Med 1978;8:283–298.
  20. Ligthart GJ, Corberand JX, Fournier C, Galanaud P, Hijmans W, Kennes B, Muller-Hermelink HK, Steinmann GG: Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 1984;28:47–55.
  21. Schoonenboom NS, Pijnenburg YA, Mulder C, Rosso SM, Van Elk EJ, Van Kamp GJ, Van Swieten JC, Scheltens P: Amyloid beta(1–42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease. Neurology 2004;62:1580–1584.
  22. Pijnenburg YA, Schoonenboom NS, Rosso SM, Mulder C, Van Kamp GJ, Van Swieten JC, Scheltens P: CSF tau and Abeta42 are not useful in the diagnosis of frontotemporal lobar degeneration. Neurology 2004;62:1649.
  23. Riemenschneider M, Wagenpfeil S, Diehl J, Lautenschlager N, Theml T, Heldmann B, Drzezga A, Jahn T, Forstl H, Kurz A: Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration. Neurology 2002;58:1622–1628.
  24. Benke T, Donnemiller E: The diagnosis of frontotemporal dementia. Fortschr Neurol Psychiatr 2002;70:243–251.
  25. Cullen KM, Halliday GM: Neurofibrillary tangles in chronic alcoholics. Neuropathol Appl Neurobiol 1995;21:312–318.
  26. Morikawa Y, Arai H, Matsushita S, Kato M, Higuchi S, Miura M, Kawakami H, Higuchi M, Okamura N, Tashiro M, Matsui T, Sasaki H: Cerebrospinal fluid tau protein levels in demented and nondemented alcoholics. Alcohol Clin Exp Res 1999;23:575–577.
  27. Zetterberg H, Andreasen N, Blennow K: Increased cerebrospinal fluid levels of transforming growth factor-beta1 in Alzheimer’s disease. Neurosci Lett 2004;367:194–196.
  28. Baggiolini M, Dahinden CA: CC chemokines in allergic inflammation. Immunol Today 1994;15:127–133.
  29. Baggiolini M: Chemokines in pathology and medicine. J Intern Med 2001;250:91–104.
  30. Lue LF, Rydel R, Brigham EF, Yang LB, Hampel H, Murphy GM Jr, Brachova L, Yan SD, Walker DG, Shen Y, Rogers J: Inflammatory repertoire of Alzheimer’s disease and nondemented elderly microglia in vitro. Glia 2001;35:72–79.
  31. Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 2003;9:453–457.
  32. Blasko I, Grubeck-Loebenstein B: Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer’s disease. Drugs Aging 2003;20:101–113.
  33. Patterson SL, Grady MS, Bothwell M: Nerve growth factor and a fibroblast growth factor-like neurotrophic activity in cerebrospinal fluid of brain injured human patients. Brain Res 1993;605:43–49.
  34. Sarchielli P, Alberti A, Floridi A, Gallai V: Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache patients. Neurology 2001;57:132–134.
  35. Humpel C, Weis C: Nerve growth factor and cholinergic CNS neurons studied in organotypic brain slices: implication in Alzheimer’s disease? J Neural Transm Suppl 2002;62:253–263.
  36. Tsuboi Y, Kakimoto K, Nakajima M, Akatsu H, Yamamoto T, Ogawa K, Ohnishi T, Daikuhara Y, Yamada T: Increased hepatocyte growth factor level in cerebrospinal fluid in Alzheimer’s disease. Acta Neurol Scand 2003;107:81–86.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50