Tau seeds catalyze fibril-type structures from GFP tau biosensor cells

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Tau protein aggregates into fibrils in Alzheimer's disease (AD) and other tauopathies.
• Prion-like seeding by tau fibrils accelerates aggregation and disease progression.

Purpose of the Study:

• To investigate whether fluorescent tau fusion proteins in biosensor cells assemble into fibril-type structures following prion-like seeding.
• To provide evidence for the fibrillar nature of tau aggregates formed in seeded biosensor cells.

Main Methods:

• Utilized biosensor cells expressing aggregation-prone tau mutants fused with fluorescent reporter proteins.
• Applied recombinant and brain-derived tau fibrils for prion-like seeding experiments.
• Analyzed cell phenotypes, sarkosyl solubility, and performed immunoelectron microscopy (ImmunoEM) on purified fibrils.

Main Results:

• Seeded biosensor cells exhibited persistent fluorescent punctated phenotypes.
• Cells with punctated phenotypes produced sarkosyl-insoluble tau fibrils, unlike non-seeded cells.
• ImmunoEM revealed GFP localization within the fuzzy coat of purified tau fibrils, confirming their structure.

Conclusions:

• The fluorescent puncta observed in seeded biosensor cells represent genuine fibril-type tau aggregates.
• These findings provide compelling evidence that tau biosensor cells can form tau fibrils through prion-like seeding.
• This validates the use of such biosensor systems for studying tau aggregation and seeding.