🧬 Tau Propagation Prion-Like Spread Simulator

Misfolded Tau Templates Normal Tau

Pathological tau conformers seed conversion of native tau.

• Microtubule stabilizer: Native tau role (axonal transport protein)
• Hyperphosphorylation: Pathological trigger (detachment from microtubules)
• Neurofibrillary tangle: Aggregate hallmark (paired helical filaments)
• MAPT: Key gene (encodes tau protein)

Placeholder: templating mechanism overview

Placeholder text: misfolded tau seeds conformational conversion of monomers.

Placeholder highlight: seeded templating is prion-like, not spontaneous.

Placeholder: why aggregates accumulate

Placeholder text: clearance pathways are overwhelmed by tau aggregates.

Release From the Affected Neuron

Pathological tau exits the donor neuron into extracellular space.

• Exosomes, free tau: Release routes (and synaptic vesicles)
• Neuronal activity: Trigger (and cell stress)
• Oligomers, fragments: Species released (seeding-competent tau)
• CSF / PET tau tracers: Detection method (biomarker assays)

Placeholder: release mechanisms

Placeholder text: exosomal and free tau release routes described here.

Placeholder highlight: activity-dependent release links network use to spread.

Uptake By a Connected Neuron

Extracellular tau seeds are internalized by a neighboring neuron.

• Endocytosis: Uptake routes (receptor-mediated entry)
• LRP1: Candidate receptor (implicated tau receptor)
• Endosomal escape: Compartment (seed reaches cytosol)
• Restarts templating: Outcome (in new cell)

Placeholder: uptake mechanism

Placeholder text: receptor-mediated endocytosis of tau seeds explained here.

Placeholder highlight: uptake completes the cell-to-cell transfer cycle.

Spread Along Neural Network Connections

Tau pathology follows synaptic connectivity, not simple diffusion.

• Connectome-based: Spread axis (not physical proximity)
• PET tau tracking: Evidence (longitudinal human studies)
• Tauopathy mouse models: Model support (seeded spread along tracts)
• High-connectivity hubs: Hub vulnerability (preferentially affected)

Placeholder: connectivity-based propagation

Placeholder text: network topology determines tau spread pathways.

Placeholder highlight: denser networks accelerate propagation across regions.

Braak-Stage Anatomical Progression Pattern

Tau pathology advances entorhinal cortex to neocortex in stereotyped order.

• Braak NFT stages I–VI: Staging scheme (Braak & Braak, 1991)
• Transentorhinal cortex: Earliest site (clinically silent stage)
• ~Stage IV–V: Dementia threshold (limbic to neocortical)
• Primary neocortex: Latest site (advanced-stage involvement)

Placeholder: six Braak NFT stages

Placeholder text: entorhinal, limbic, and neocortical stage progression.

Placeholder highlight: staging correlates with cognitive decline severity.

Braak NFT stage → region → clinical correlate