Related Experiment Video
Updated: Jun 14, 2026
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Characterization of tau fibrillization in vitro
Shaohua Xu1, Kurt R Brunden, John Q Trojanowski
1The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA.
Summary
Researchers observed how normal tau proteins transform into fibrils, the cause of neurofibrillary tangles in Alzheimer's disease. Understanding tau assembly provides insights into potential treatments for neurodegenerative disorders.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Tau protein assembly into paired helical filaments forms neurofibrillary tangles, a hallmark of Alzheimer's disease and tauopathies.
- Understanding tau assembly is crucial for identifying therapeutic targets for Alzheimer's disease and related disorders.
- This study investigated the conversion of normal soluble tau into tau fibrils using recombinant human tau.
Purpose of the Study:
- To delineate the events involved in the conversion of soluble tau into tau fibrils.
- To characterize the structural intermediates and morphologies of tau assemblies during fibrillization.
Main Methods:
- Utilized atomic force microscopy (AFM) and transmission electron microscopy (TEM).
- Analyzed tau assemblies formed by incubating soluble tau with heparin over time.
Main Results:
- Tau initially oligomerizes into spherical units (18-21 nm) that form nascent fibrils.
- Observed the formation of 'string of beads' structures, evolving into straight, twisted, and paired helical filaments.
- Identified three fundamental axial structural features in later-stage fibril cross-sections.
Conclusions:
- Tau fibrillization produces diverse filament morphologies, with different structural species coexisting.
- Temporal analysis reveals the generation of structural intermediates during tau fibrillization.
- The observed tau fibrils closely resemble authentic human tauopathy filaments.
