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Pre-aggregated Aβ1–42 peptide increases tau aggregation and hyperphosphorylation after short-term application

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Abstract

Neuritic amyloid plaques and neurofibrillary tangles, consisting of hyperphosphorylated tau protein, are the hallmarks of Alzheimer disease. It is not clear so far, how both structures are functionally and physiologically connected. We have investigated the role of Aβ1–42 on hyperphosphorylation and aggregation of tau in SY5Y cells by transfection and overexpression with two tau constructs, a shortened wildtype tau (2N4R) and a point mutation tau (P301L), found in fronto-temporal dementia. It was found that the tau protein becomes hyperphosphorylated and forms large aggregates inside cells, visualized by immunofluorescence, after short incubation of 90 min with preaggregated Aβ1–42. In Addition, Aβ1–42 caused a decrease of tau solubility in both tau constructs in this relatively short time period. Taken together, these experiments suggest that pathological preaggregated Aβ1–42 in physiological concentrations quickly induces hyperphosphorylation and pathological structural changes of tau protein and thereby directly linking the ‘amyloid hypothesis’ to tau pathology, observed in Alzheimer disease.

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Acknowledgments

This study was supported by the Department of Psychiatry from the University Hospital Erlangen. We thank Dr. G. Hübinger, Sirenade, for providing the P301L and 2N4R tau constructs.

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Authors and Affiliations

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

    Sabine Ott, Andreas Wolfram Henkel, Maria Kerstin Henkel & Johannes Kornhuber

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

    Andreas Wolfram Henkel & Zoran B. Redzic

  3. Department of Psychiatry and Psychotherapy, LVR-Clinic Essen, University of Duisburg, Essen, Germany

    Jens Wiltfang

Authors
  1. Sabine Ott
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  2. Andreas Wolfram Henkel
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  3. Maria Kerstin Henkel
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  5. Johannes Kornhuber
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Correspondence to Andreas Wolfram Henkel.

Additional information

S. Ott and A. W. Henkel contributed equally to this work.

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Ott, S., Henkel, A.W., Henkel, M.K. et al. Pre-aggregated Aβ1–42 peptide increases tau aggregation and hyperphosphorylation after short-term application. Mol Cell Biochem 349, 169–177 (2011). https://doi.org/10.1007/s11010-010-0671-7

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  • DOI: https://doi.org/10.1007/s11010-010-0671-7

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