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Journal of Neural Transmission

, Volume 116, Issue 2, pp 203–212 | Cite as

Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease

  • Volker Welge
  • Oliver Fiege
  • Piotr Lewczuk
  • Brit Mollenhauer
  • Hermann Esselmann
  • Hans-Wolfgang Klafki
  • Stefanie Wolf
  • Claudia Trenkwalder
  • Markus Otto
  • Johannes Kornhuber
  • Jens Wiltfang
  • Mirko Bibl
Alzheimer's Disease and Related Disorders - Original Article

Abstract

Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer’s disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Aβ1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Aβ1-42/Aβ1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Aβ1-42/Aβ1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Aβ1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Aβ1-42/Aβ1-38. The ratio Aβ1-42/Aβ1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker.

Keywords

Alzheimer’s disease Cerebrospinal fluid Amyloid-β peptides Biomarkers ELISA Electrochemiluminescence 

Abbreviations

Aβ peptides

Amyloid-beta peptides

Aβ-SDS-PAGE/immunoblot

Amyloid-beta-sodium-dodecyl-sulphate-polyacrylamide-gel electrophoresis with western immunoblot

AD

Alzheimer’s disease

CSF

Cerebrospinal fluid

DCC

Depressive cognitive complainers

ELISA

Enzyme linked immunosorbent assay

MMSE

Mini-mental-status examination

NINCDS-ADRDA

National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association

NINDS-SPSP

National Institute of Neurological Disorders and Stroke and the Society for PSP

Notes

Acknowledgments

This study was supported by the following grants from the German Federal Ministry of Education and Research (BMBF): Kompetenznetz Demenzen (01 GI 0420), HBPP-NGFN2 (01 GR 0447), and the Forschungsnetz der Früh- und Differenzialdiagnose der Creutzfeldt-Jakob-Krankheit und der neuen Variante der CJK (01 GI 0301), and by the EU grants cNEUPRO (contract no. LSHM-CT-2007-037950), and neuroTAS (contract no. LSHB-CT-2006-037953). MB was supported by the Research program, Faculty of medicine, Georg-August-University Göttingen. MO was supported by grants from the German Federal Ministry of Education (German CJD therapy study FK 01KO0506), EU (anteprion 019090) and Landesstiftung Baden Württemberg).The authors would like to thank Sabine Paul, Birgit Otte and Heike Zech for excellent technical assistance.

Conflict of interest statement

There are no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the work submitted that could have inappropriately influenced (bias) our work. The study was conducted under the guidelines of the Declaration of Helsinki (World medical Organisation 1996) and approved by the ethics committee of the University of Goettingen and Hessen.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Volker Welge
    • 1
  • Oliver Fiege
    • 1
  • Piotr Lewczuk
    • 2
  • Brit Mollenhauer
    • 3
  • Hermann Esselmann
    • 2
  • Hans-Wolfgang Klafki
    • 1
  • Stefanie Wolf
    • 3
  • Claudia Trenkwalder
    • 4
  • Markus Otto
    • 5
  • Johannes Kornhuber
    • 2
  • Jens Wiltfang
    • 1
  • Mirko Bibl
    • 1
  1. 1.Klinik für Psychiatrie und PsychotherapieUniversität Duisburg-EssenEssenGermany
  2. 2.Department of Psychiatry and PsychotherapyUniversity of Erlangen-NurembergErlangenGermany
  3. 3.Department of PsychiatryUniversity of GoettingenGöttingenGermany
  4. 4.University of GoettingenKasselGermany
  5. 5.Department of NeurologyUniversity of UlmUlmGermany

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