Abstract
We report here that aggregated beta-amyloid (Abeta) 1-42 promotes tau aggregation in vitro in a dose-dependent manner. When Abeta-mediated aggregated tau was used as a substrate for tau protein kinase II (TPK II), an 8-fold increase in the rate of TPK II-mediated tau phosphorylation was observed. The extent of TPK II-dependent tau phosphorylation increased as a function of time and Abeta 1-42 concentration, and hyperphosphorylated tau was found to be decorated with an Alzheimer's disease-related phosphoepitope (P-Thr-231). In HEK 293 cells co-expressing CT-100 amyloid precursor protein and tau, the release of Abeta 1-42 from these cells was impaired. Taken together, these in vitro results suggest that Abeta 1-42 promotes both tau aggregation and hyperphosphorylation.
MeSH terms
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / chemistry*
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Peptides / pharmacology
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Cattle
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Cell Line
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Cyclin-Dependent Kinase 5
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Dose-Response Relationship, Drug
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Epitopes / chemistry
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Epitopes / drug effects
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Epitopes / metabolism
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Genes, Reporter
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Humans
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Kidney / cytology
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Kidney / metabolism
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Macromolecular Substances
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Peptide Fragments / chemistry*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism*
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Peptide Fragments / pharmacology
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Phosphorylation / drug effects
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Protein Binding / drug effects
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Protein Binding / physiology
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Solubility / drug effects
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tau Proteins / chemistry*
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tau Proteins / genetics
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tau Proteins / metabolism*
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Epitopes
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Macromolecular Substances
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Peptide Fragments
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Recombinant Fusion Proteins
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Recombinant Proteins
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amyloid beta-protein (1-42)
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tau Proteins
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Cyclin-Dependent Kinase 5
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Protein Serine-Threonine Kinases
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tau protein kinase II