HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 41, 40162-40168, October 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/41/40162    most recent M308243200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferrari, A. Articles by Götz, J. Search for Related Content PubMed PubMed Citation Articles by Ferrari, A. Articles by Götz, J. Social Bookmarking                      What's this?

-Amyloid Induces Paired Helical Filament-like Tau Filaments in Tissue Culture^*

Alessandra Ferrari  , Frederic Hoerndli , Thomas Baechi ¶, Roger M. Nitsch  and Jürgen Götz  ||

From the Division of Psychiatry Research, University of Zürich, August Forel Strasse 1, 8008 Zürich and the ^¶Central Laboratory for Electron Microscopy, University of Zurich, Gloriastrasse 30, 8028 Zurich, Switzerland

Paired helical filaments (PHF) are the principal pathologic components of neurofibrillary tangles in Alzheimer's disease (AD). To reproduce the formation of PHF in tissue culture, we stably expressed human tau with and without pathogenic mutations in human SH-SY5Y cells and exposed them for 5 days to aggregated synthetic -amyloid peptide (A₄₂). This caused a decreased solubility of tau along with the generation of PHF-like tau-containing filaments. These were 20 nm wide and had periodicities of 130-140 nm in the presence of P301L mutant tau or 150-160 nm in the presence of wild-type tau. Mutagenesis of the phosphoepitope serine 422 of tau prevented both the A₄₂-mediated decrease in solubility and the generation of PHF-like filaments, suggesting a role of serine 422 or its phosphorylation in tau filament formation. Together, our data underscore a role of A₄₂ in the formation of PHF-like filaments. Our culture system will be useful to map phosphoepitopes of tau involved in PHF formation and to identify and characterize modifiers of the tau pathology. Further adaptation of the system may allow the screening and validation of compounds designed to prevent PHF formation.

Received for publication, July 29, 2003

^* This research was supported in part by grants from the Swiss National Science Foundation, the Hartmann Müller Fund, the Olga Mayenfisch Foundation, the Alzheimer and Depression (A+D) Fonds of the Swiss Academy of Medical Sciences, and by the National Center of Competence in Research "Neuronal plasticity and repair." The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Medical Research Council Laboratory for Molecular Cell Biology, University College of London, Gower St., London WC1E 6BT, United Kingdom.

^|| To whom correspondence should be addressed: Division of Psychiatry Research, University of Zürich, August Forel Str. 1, 8008 Zürich, Switzerland. Tel: 41-1-634-8873; Fax: 41-1-634-8874; E-mail: goetz{at}bli.unizh.ch.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. P. Hanger, H. L. Byers, S. Wray, K.-Y. Leung, M. J. Saxton, A. Seereeram, C. H. Reynolds, M. A. Ward, and B. H. Anderton Novel Phosphorylation Sites in Tau from Alzheimer Brain Support a Role for Casein Kinase 1 in Disease Pathogenesis J. Biol. Chem., August 10, 2007; 282(32): 23645 - 23654. [Abstract] [Full Text] [PDF]

				A. I. Iliev, S. Ganesan, G. Bunt, and F. S. Wouters Removal of Pattern-breaking Sequences in Microtubule Binding Repeats Produces Instantaneous Tau Aggregation and Toxicity J. Biol. Chem., December 1, 2006; 281(48): 37195 - 37204. [Abstract] [Full Text] [PDF]

				H. Ding, T. A. Matthews, and G. V. W. Johnson Site-specific Phosphorylation and Caspase Cleavage Differentially Impact Tau-Microtubule Interactions and Tau Aggregation J. Biol. Chem., July 14, 2006; 281(28): 19107 - 19114. [Abstract] [Full Text] [PDF]

				I. Khlistunova, J. Biernat, Y. Wang, M. Pickhardt, M. von Bergen, Z. Gazova, E. Mandelkow, and E.-M. Mandelkow Inducible Expression of Tau Repeat Domain in Cell Models of Tauopathy: AGGREGATION IS TOXIC TO CELLS BUT CAN BE REVERSED BY INHIBITOR DRUGS J. Biol. Chem., January 13, 2006; 281(2): 1205 - 1214. [Abstract] [Full Text] [PDF]

				M. Pickhardt, Z. Gazova, M. von Bergen, I. Khlistunova, Y. Wang, A. Hascher, E.-M. Mandelkow, J. Biernat, and E. Mandelkow Anthraquinones Inhibit Tau Aggregation and Dissolve Alzheimer's Paired Helical Filaments in Vitro and in Cells J. Biol. Chem., February 4, 2005; 280(5): 3628 - 3635. [Abstract] [Full Text] [PDF]

				G. V. W. Johnson and W. H. Stoothoff Tau phosphorylation in neuronal cell function and dysfunction J. Cell Sci., November 15, 2004; 117(24): 5721 - 5729. [Abstract] [Full Text] [PDF]

				T. D. Stein, N. J. Anders, C. DeCarli, S. L. Chan, M. P. Mattson, and J. A. Johnson Neutralization of Transthyretin Reverses the Neuroprotective Effects of Secreted Amyloid Precursor Protein (APP) in APPSw Mice Resulting in Tau Phosphorylation and Loss of Hippocampal Neurons: Support for the Amyloid Hypothesis J. Neurosci., September 1, 2004; 24(35): 7707 - 7717. [Abstract] [Full Text] [PDF]