🧬 Tau Protein Tangle Formation Mechanism Simulator

Normal Tau — Microtubule Stabilization

Placeholder: tau normally stabilizes axonal microtubule tracks.

• 6: Tau isoforms (CNS) (Placeholder splice variant note)
• 3R/4R: Microtubule binding repeats (Placeholder repeat domain note)
• Low: Normal phosphate sites (Placeholder baseline phosphorylation)
• Stable: Axonal transport (Placeholder transport status)

Tau structure and normal function

Placeholder short paragraph on native tau-microtubule binding.

Tau Hyperphosphorylation

Placeholder: kinase/phosphatase imbalance hyperphosphorylates tau.

• GSK-3β, CDK5: Key kinases (Placeholder kinase list)
• >80: Phospho-sites (AD) (Placeholder site count)
• Reduced: Phosphatase activity (Placeholder PP2A note)
• AT8 epitope: Onset marker (Placeholder biomarker note)

Kinase-phosphatase imbalance

Placeholder short paragraph on hyperphosphorylation cascade.

Detachment from Microtubules

Placeholder: phosphorylated tau detaches, destabilizing microtubules.

• High: Binding affinity loss (Placeholder affinity change)
• Falling: Microtubule integrity (Placeholder integrity metric)
• Rising: Free cytosolic tau (Placeholder pool increase)
• Present: Axonal transport defect (Placeholder transport note)

Loss of microtubule affinity

Placeholder short paragraph on detachment mechanism.

Tau Aggregation into Tangles

Placeholder: detached tau misfolds into paired helical filaments.

• PHF: Filament type (Placeholder paired helical filament note)
• β-sheet: Core structure (Placeholder cross-β note)
• Prion-like: Seeding behavior (Placeholder propagation note)
• Oligomers: Aggregation nucleus (Placeholder nucleation note)

Paired helical filament formation

Placeholder short paragraph on tau aggregation mechanism.

Neurofibrillary Tangle Accumulation & Neuronal Dysfunction

Placeholder: NFTs accumulate and impair neuronal function.

• I–VI: Braak staging range (Placeholder staging note)
• Progressive: Synaptic loss (Placeholder synapse note)
• Trans-synaptic: Spread pattern (Placeholder spread note)
• Strong: Clinical correlation (Placeholder cognitive correlation)

Tangle burden and neuronal dysfunction

Placeholder short paragraph on NFT accumulation and decline.

Placeholder key insight on Braak staging and cognitive decline.