Related Experiment Video
Updated: Nov 13, 2025
Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue
Lauren V C Miller1, Aamir S Mukadam1, Claire S Durrant2,3
1Department of Clinical Neurosciences, UK Dementia Research Institute at the University of Cambridge, Cambridge, UK.
Abstract:
A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour. We used organotypic hippocampal slice cultures from P301S tau transgenic mice in order to precisely control the concentration of extracellular tau assemblies in neural tissue. Whilst untreated slices displayed no overt signs of pathology, exposure to recombinant tau assemblies could result in the formation of intraneuronal, hyperphosphorylated tau structures. However, seeding ability of tau assemblies did not titrate in a one-hit manner in neural tissue. The results suggest that seeding behaviour of tau arises at high concentrations, with implications for the interpretation of high-dose intracranial challenge experiments and the possible contribution of seeded aggregation to human disease.
Insights
Tau protein assemblies, implicated in neurodegenerative diseases, do not behave like classical infectious particles. Their seeding activity in neural tissue requires high concentrations, challenging current disease models.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Protein tau assemblies are implicated in the spread of neurodegenerative diseases.
- Infectious agents typically act as independent particles.
Purpose of the Study:
- To investigate if tau assemblies exhibit particulate behavior characteristic of infectious agents.
- To determine the dose-dependent seeding activity of tau assemblies in neural tissue.
Main Methods:
- Organotypic hippocampal slice cultures from P301S tau transgenic mice were used.
- Controlled exposure to recombinant tau assemblies to assess seeding potential.
- Monitoring for the formation of intraneuronal, hyperphosphorylated tau structures.
Main Results:
- Exposure to tau assemblies induced hyperphosphorylated tau structures in slices.
- Tau assembly seeding activity did not follow a simple one-hit titration model.
- Seeding behavior was observed primarily at high concentrations of tau assemblies.
Conclusions:
- Tau assembly seeding in neural tissue is concentration-dependent and not strictly particulate.
- Findings impact the interpretation of high-dose challenge experiments in neurodegeneration research.
- The role of seeded aggregation in human tauopathies requires further investigation considering concentration effects.
More Related Videos
12:57Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
09:32Bioluminescence Imaging of Neuroinflammation in Transgenic Mice After Peripheral Inoculation of Alpha-Synuclein Fibrils
Published on: April 13, 2017
