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.