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

  • Alzheimer's Disease and Related Disorders - Original Article
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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.

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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

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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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Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie, Universität Duisburg-Essen, Rheinische Kliniken Essen, Virchowstr. 174, 45147, Essen, Germany

    Volker Welge, Oliver Fiege, Hans-Wolfgang Klafki, Jens Wiltfang & Mirko Bibl

  2. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Piotr Lewczuk, Hermann Esselmann & Johannes Kornhuber

  3. Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075, Göttingen, Germany

    Brit Mollenhauer & Stefanie Wolf

  4. University of Goettingen, Paracelsus-Elena Klinik, Kassel, Germany

    Claudia Trenkwalder

  5. Department of Neurology, University of Ulm, Steinhövelstr. 1, Ulm, Germany

    Markus Otto

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  1. Volker Welge
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  2. Oliver Fiege
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Correspondence to Mirko Bibl.

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Welge, V., Fiege, O., Lewczuk, P. et al. Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease. J Neural Transm 116, 203–212 (2009). https://doi.org/10.1007/s00702-008-0177-6

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  • DOI: https://doi.org/10.1007/s00702-008-0177-6

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