Related Experiment Videos
Evidence for an intermediate in tau filament formation
1Biophysics Program, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Biochemistry
|February 11, 2004
Summary
Anionic surfactants promote Alzheimer's disease tau fibrillization by forming negatively charged surfaces that accelerate aggregation. This process involves an intermediate stage before filament formation, crucial for understanding tau pathology.
Area of Science:
- Neuroscience
- Biochemistry
- Materials Science
Background:
- Alzheimer's disease is characterized by intraneuronal tau protein filaments.
- Tau fibrillization can be induced in vitro by agents like anionic surfactants.
- Understanding the mechanism of tau fibrillization is key to developing therapeutic strategies.
Purpose of the Study:
- To elucidate the pathway of tau fibrillization induced by anionic surfactants.
- To investigate the role of anionic surfaces in tau aggregation.
- To characterize the intermediate species formed during fibrillization.
Main Methods:
- Electron microscopy
- Fluorescence spectroscopy
- Thioflavin S binding assays
- Experiments with anionic polystyrene microspheres
Main Results:
- Anionic surfactants and tau protein form micelles, creating negatively charged surfaces for tau aggregation.
- A non-filamentous, thioflavin S reactive intermediate forms over hours on these surfaces.
- Fibrillization follows nucleation-dependent kinetics, with lag and exponential phases, reaching equilibrium in ~24 hours.
- The process does not require protein insertion into micelles or mixed micelle formation.
Conclusions:
- Anionic surfaces are critical for initiating and promoting tau fibrillization.
- The proposed pathway involving amorphous aggregation, intermediate formation, and fibrillization may be relevant for other tau inducers and in vivo processes.
- This study provides insights into the fundamental mechanisms of tau pathology in Alzheimer's disease.