Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Rodents and transgenic models do not exhibit Alzheimer's disease (AD)-like neurofibrillary pathology.
• The inability of murine tau to self-assemble into filaments is a potential reason for this absence.
• Understanding tau filament formation is crucial for AD research.

Purpose of the Study:

• To compare the filament-forming abilities of recombinant murine and human tau proteins.
• To investigate if hyperphosphorylation induces self-assembly in murine tau.
• To determine if murine tau can form AD-like pathological structures.

Main Methods:

• Recombinant human and murine tau (0N4R) proteins were generated.
• Proteins were hyperphosphorylated in vitro using rat brain extract as a kinase source.
• Filament formation and morphology were analyzed after hyperphosphorylation.

Main Results:

• Murine tau undergoes hyperphosphorylation with similar stoichiometry and patterns as human tau.
• Hyperphosphorylated murine tau self-assembles into paired helical and straight filament-like structures.
• Approximately 60-70% of hyperphosphorylated murine tau aggregated, similar to human tau.

Conclusions:

• Murine tau can form AD-like neurofibrillary pathology upon hyperphosphorylation.
• This finding suggests that murine tau has the intrinsic ability to self-assemble into filaments.
• Rodent models may be viable for studying tauopathies if appropriate hyperphosphorylation is induced.