Original Research Article
Tau Protein, Aβ42 and S-100B Protein in Cerebrospinal Fluid of Patients with Dementia with Lewy BodiesMollenhauer B.a · Cepek L.a · Bibl M.b · Wiltfang J.d · Schulz-Schaeffer W.J.c · Ciesielczyk B.a · Neumann M.e · Steinacker P.b · Kretzschmar H.A.e · Poser S.a · Trenkwalder C.f · Otto M.a
Departments of aNeurology, bPsychiatry and cNeuropathology, Georg August University Göttingen, Göttingen, dDepartment of Psychiatry, Friedrich Alexander University Erlangen/Nuremberg, Erlangen, eDepartment of Neuropathology, Ludwig Maximilians University Munich, Munich, and fGeorg August University Göttingen, Paracelsus-Elena-Klinik, Kassel, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and β-amyloid(1–42) (Aβ42), promising results for the diagnosis of Alzheimer’s disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Aβ42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases.
© 2005 S. Karger AG, Basel
- McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): Report of the consortium on DLB international workshop. Neurology 1996;47:1113–1124.
- McKeith I, Fairbairn A, Perry R, Thompson P, Perry E: Neuroleptic sensitivity in patients with senile dementia of the Lewy-body type. BMJ 1992;305:673–678.
- Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green R, et al: Reduction of β-amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 1995;38:643–648.
- Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H: Improved discrimination of AD-patients using β-amyloid (1–42) and tau levels in CSF. Neurology 1999;52:1555–1562.
- Galasko D: Cerebrospinal fluid levels of A beta 42 and tau: Potential markers of Alzheimer’s disease. J Neural Transm Suppl 1998;53:209–221.
- Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, Bergeson J, Manetti GJ, Zimmermann M, Tang B, Bartko JJ, Cohen RM: Decreased beta-amyloid 1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094–3003.
- Otto M, Wiltfang J, Tumani H, Zerr I, Lantsch M, Kornhuber J, Weber T, Kretzschmar HA, Poser S: Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 1997;225:210–212.
- Otto M, Wiltfang J, Cepek L, Neumann M, Mollenhauer B, Steinacker P, Ciesielczyk B, Schulz-Schaeffer W, Kretzschmar HA, Poser S: Tau protein and 14–3–3 protein in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 2002;58:192–197.
- Berger RP, Pierce MC, Wisniewski SR, Adelson PD, Clark RS, Ruppel RA, Kochanek PM: Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics 2002;109:E31.
- Peskind ER, Griffin WS, Akama KT, Raskind MA, Van Eldik LJ: Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer’s disease. Neurochem Int 2001;39:409–413.
- Green AJ, Harvey RJ, Thompson EJ, Rossor MN: Increased S100beta in the cerebrospinal fluid of patients with frontotemporal dementia. Neurosci Lett 1997;235:5–8.
- Maeck L, Meller J, Otto M, Stiens G, Wiltfang J, Stoppe G: A beta peptide 1–42, Tau protein and S-100B protein level in cerebrospinal fluid of three patients with primary progressive aphasia. Neurosci Lett 2002;333:33–36.
- Sussmuth SD, Tumani H, Ecker D, Ludolph AC: Amyotrophic lateral sclerosis: Disease stage related changes of tau protein and S100 beta in cerebrospinal fluid and creatine kinase in serum. Neurosci Lett 2003;353:57–60.
- Otto M, Stein H, Szudra A, Zerr I, Bodemer M, Gefeller O, Poser S, Kretzschmar HA, Mader M, Weber T: S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol 1997;244:566–570.
- Kanemaru K, Kameda N, Yamanouchi H: Decreased CSF amyloid β42 and normal tau levels in dementia with Lewy bodies. Neurology 2000;54:1875–1876.
- Gomez-Tortosa E, Gonzalo I, Fanjul S, Sainz MJ, Cantarero S, Cemillan C, Yebenes JG, del Ser T: Cerebrospinal fluid markers in dementia with Lewy bodies compared with Alzheimer disease. Arch Neurol 2003;60:1218–1222.
- Tschampa HJ, Schulz-Schaeffer W, Wiltfang J, Poser S, Otto M, Neumann M, Kretzschmar HA: Decreased CSF amyloid 42 and normal tau levels in dementia with Lewy bodies. Neurology 2001;56:576.
- Folstein MF, Folstein SE, McHugh PR: ‘Mini-mental state’: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
- 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.
- Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, Kholodenko D, Motter R, Sherrington R, Perry B, Yao H, Strome R, Lieberburg I, Rommens J, Kim S, Schenk D, Fraser P, St George Hyslop P, Selkoe DJ: Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat Med 1997;3:67–72.
- Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, Kholodenko D, Motter R, Sherrington R, Perry B, Yao H, Strome R, Lieberburg I, Rommens J, Kim S, Schenk D, Fraser P, St George Hyslop P, Selkoe DJ: Amyloid precursor protein processing and Aβ42 deposition in transgenic mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 1997;94:1550–1555.
- Aurell A, Rosengren LE, Wikkelsö C, Nordberg G, Haglid KG: The S-100 protein in cerebrospinal fluid: A simple ELISA method. J Neurol Sci 1998;89:157–164.
- Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Matsushita S, Machida N, Nakagawa T, Lee VM, Trojanowski JQ, Sasaki H: Effect of genetic risk factors and disease progression on the cerebrospinal fluid tau levels in Alzheimer’s disease. J Am Geriatr Soc 1997;45:1228–1231.
- Molina L, Touchon J, Herpe M, Lefranc D, Duplan L, Cristol JP, Sabatier R, Vermersch P, Pau B, Mourton-Gilles C: Tau and Apo E in CSF: Potential aid for discriminating Alzheimer’s disease from other dementias. Neuroreport 1999;10:3491–3495.
- Sjogren M, Davidsson P, Tullberg M, Minthon L, Wallin A, Wikkelso C, Granerus AK, Vanderstichele H, Vanmechelen E, Blennow K: CSF levels of tau, beta-amyloid (1–42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging. J Neural Transm 2000;107:563–579.
Parnetti L, Lanari A, Amici S, Gallai V, Vanmechelen E, Hulstaert F: CSF phosphorylated tau is a possible marker for discriminating Alzheimer’s disease from dementia with Lewy bodies. Phospho-Tau International Study Group. Neurol Sci 2001;22:77–78.
- Arai H, Higuchi S, Muramatsu T, Iwatsubo T, Sasaki H, Tronajowski JQ: Apolipoprotein E gene in diffuse Lewy body disease with or without co-existing Alzheimer’s disease. Lancet 1994;344:1307.
- Mollenhauer B, Serafin S, Zerr I, Steinhoff BJ, Otto M, Scherer M, Schulz-Schaeffer WJ, Poser S: Diagnostic problems during late course in Creutzfeldt-Jakob disease. J Neurol 2002;250:629–630.
- Watson GS, Peskind ER, Asthana S, Purganan K, Wait C, Chapman D, Schwartz MW, Plymate S, Craft S: Insulin increases CSF Aβ42 levels in normal older adults. Neurology 2003;60:1899–1903.
- Hansen LA, Samuel W: Criteria for Alzheimer’s disease and the nosology of dementia with Lewy bodies. Neurology 1997;48:126–132.
- Braak H, Braak E: Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 1991;82:239–259.
- Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, Thal LJ, Corey-Bloom J: Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 2003;60:1586–1590.
- Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, Buerger K, Wiltfang J, Otto M, Kretzschmar H, Moeller HJ, Imagawa M, Kohno H, Nakashima K, Kuzuhara S, Sasaki H, Imahori K: Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for antemortem diagnosis of Alzheimer’s disease. Ann Neurol 2001;50:150–156.
- 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 peptide 42. Arch Neurol 2003;60:1202–1206.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: 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.
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 government 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.