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Immuno-PCR-based quantification of multiple phosphorylated tau-epitopes linked to Alzheimer’s disease

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An Erratum to this article was published on 10 November 2009

Abstract

Several lines of evidence suggest that quantification of phosphorylated sites in the tau-protein (phospho-τ) might be favorable for early and specific Alzheimer’s disease diagnosis. The typical setup to quantify phosphorylated τ-epitopes relies on a sandwich ELISA with a capture antibody (Ab) recognizing τ independent of its phosphorylation status and a detector Ab binding specifically to a certain phosphorylation site. Besides Ab specificities, major challenges arise from the very low τ-concentrations in cerebrospinal fluid (CSF) ranging from 100 to 2,000 pg/ml. Based on the phosphorylation degree of a given position, which can be below 10%, the corresponding phospho-τ-level might be much lower, especially for multiphosphorylated epitopes studied here. Thus, a novel, highly sensitive, and generally applicable immunoassay is described to quantify τ-versions, which are phosphorylated at pThr212/pSer214/pThr231/pSer235, down to τ-concentrations of 2 pg/ml in CSF.

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Acknowledgement

We thank Carolyn Zimmermann for proofreading.

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Authors and Affiliations

  1. Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Faculty of Chemistry and Mineralogy, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany

    David Singer & Ralf Hoffmann

  2. Department of Neurology, Kuopio University, Yliopistonranta 1E, 70211, Kuopio, Finland

    Hilkka Soininen

  3. Section of Neuropathology, Kuopio University, Yliopistonranta 1E, 70211, Kuopio, Finland

    Irina Alafuzoff

Authors
  1. David Singer
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  2. Hilkka Soininen
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  3. Irina Alafuzoff
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  4. Ralf Hoffmann
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Corresponding author

Correspondence to Ralf Hoffmann.

Additional information

This work was funded by the Deutsche Forschungsgemeinschaft (DFG) (grant 2222/3-1), the European Fund for Regional Structure Development (EFRE), and the “Industrie-und Handelskammer zu Leipzig.”

An erratum to this article can be found at http://dx.doi.org/10.1007/s00216-009-3259-x

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Singer, D., Soininen, H., Alafuzoff, I. et al. Immuno-PCR-based quantification of multiple phosphorylated tau-epitopes linked to Alzheimer’s disease. Anal Bioanal Chem 395, 2263–2267 (2009). https://doi.org/10.1007/s00216-009-3208-8

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  • DOI: https://doi.org/10.1007/s00216-009-3208-8

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