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Multidimensional plasma protein separation technique for identification of potential Alzheimer’s disease plasma biomarkers: a pilot study

  • Dementias - Original Article
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Abstract

Neurochemical differential diagnosis between Alzheimer’s disease and other dementias is currently based on CSF biomarkers. Here, we report a method by which potential biomarkers can be identified in blood. Blood plasma samples from seven well-characterized Alzheimer’s patients and seven non-Alzheimer’s patients were subjected to a multi-dimensional protein separation procedure. After removal of 12 high-abundance proteins, the depleted samples from both diagnostic groups were labeled with different fluorescent dyes, mixed and separated by anion exchange and RP-chromatography. The resulting chromatography fractions were analyzed on 2D-gels. Twenty significant differentially expressed proteins were identified by mass spectrometry analysis. Ten of these proteins were either involved in the pathophysiology of Alzheimer’s disease or the amyloid/Aβ-peptide processing pathway. This work demonstrated a successful application of a multidimensional separation technique and holds the potential to identifying blood-based biomarkers for other diseases in the future.

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Abbreviations

CSF:

Cerebral spinal fluid

AD:

Alzheimer’s disease

nAD:

Non-Alzheimer’s disease

ELISA:

Enzyme-linked immunosorbent assay

MCI:

Mild cognitive impairment

NINCDS-ADRDA:

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

CV:

Column volumes

MRI:

Magnetic resonance imaging

CT:

Computer tomography

DOC:

Deoxycholate

TCA:

Trichloroacetic acid

RPC:

Reversed-phase chromatography

LC:

Liquid chromatography

ESI-MS:

Electrospray ionization mass spectrometry

DIGE:

Difference gel electrophoresis

MS:

Mass spectrometry

BVA:

Biological variation analysis

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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 European Commission (cNeupro, NeuroTAS).

Conflict of interest

All authors declare no conflict of financial or economic interests.

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Jabriya, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait

    Andreas Wolfram Henkel

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

    Andreas Wolfram Henkel, Katharina Müller, Piotr Lewczuk & Johannes Kornhuber

  3. Department of Psychiatry and Psychotherapy, University of Duisburg Essen, Virchowstrasse 174, 45147, Essen, Germany

    Jens Wiltfang

  4. Medical Proteome Center, Ruhr-University of Bochum, Universitätsstrasse 150, 44801, Bochum, Germany

    Thorsten Müller & Katrin Marcus

Authors
  1. Andreas Wolfram Henkel
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  2. Katharina Müller
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  3. Piotr Lewczuk
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  4. Thorsten Müller
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  5. Katrin Marcus
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  6. Johannes Kornhuber
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  7. Jens Wiltfang
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Correspondence to Andreas Wolfram Henkel.

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Andreas Wolfram Henkel and Katharina Müller contributed equally to this paper.

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Henkel, A.W., Müller, K., Lewczuk, P. et al. Multidimensional plasma protein separation technique for identification of potential Alzheimer’s disease plasma biomarkers: a pilot study. J Neural Transm 119, 779–788 (2012). https://doi.org/10.1007/s00702-012-0781-3

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  • DOI: https://doi.org/10.1007/s00702-012-0781-3

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