β-amyloid induces paired helical filament-like tau filaments in tissue culture

Ferrari, Alessandra, Hoerndli, Frederic, Baechi, Thomas, Nitsch, Roger M. and Gotz, Juergen (2003) β-amyloid induces paired helical filament-like tau filaments in tissue culture. Journal of Biological Chemistry, 278 41: 40162-40168. doi:10.1074/jbc.M308243200

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Author Ferrari, Alessandra
Hoerndli, Frederic
Baechi, Thomas
Nitsch, Roger M.
Gotz, Juergen
Title β-amyloid induces paired helical filament-like tau filaments in tissue culture
Formatted title
β-amyloid induces paired helical filament-like tau filaments in tissue culture
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2003-10-10
Sub-type Article (original research)
DOI 10.1074/jbc.M308243200
Open Access Status File (Publisher version)
Volume 278
Issue 41
Start page 40162
End page 40168
Total pages 7
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
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 β-amyloid peptide (Aβ42). 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 Aβ42-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 Aβ42 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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