{{Infobox
| infobox-header = Phosphorylated Tau Protein
| infobox-subheader = Hyperphosphorylated Tau in NFT Formation
| label1 = Gene
| data1 = MAPT
| label2 = UniProt ID
| data2 = P10636 (Tau-2)
| label3 = Alternative Names
| data3 = PHF-tau, AT8, AT180, AT270, p-tau
| label4 = Isoforms
| data4 = 6 major isoforms (352-441 amino acids)
| label5 = Phosphorylation Sites
| data5 = >85 sites identified; key sites: Ser202, Thr205, Ser396, Ser404
| label6 = Aggregation State
| data6 = Forms paired helical filaments (PHFs) and straight filaments (SFs)
| label7 = Pathological Form
| data7 = Neurofibrillary tangles (NFTs), pretangles, threads
}}
Phosphorylated Tau Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Phosphorylated tau (p-tau) refers to the hyperphosphorylated form of the microtubule-associated protein tau (MAPT). Unlike normal tau, p-tau aggregates into neurofibrillary tangles (NFTs), one of the hallmark pathological lesions in Alzheimer's disease and other tauopathies.
In AD and tauopathies, tau becomes hyperphosphorylated (>10 mol phosphate/mol tau):
Key kinases overactive in AD:
Key phosphatases downregulated:
| Epitope | Antibody | Disease Specificity |
|---|---|---|
| Ser202/Thr205 | AT8 | Early NFT formation |
| Thr231 | AT180 | Intermediate NFT |
| Ser396/Ser404 | PHF-13 | Late stage NFT |
| Ser422 | pS422 | AD-specific |
| Marker | Clinical Utility |
|---|---|
| p-tau181 | Distinguishes AD from other dementias; correlates with NFT burden |
| p-tau217 | Higher specificity for AD; detects earlier |
| p-tau231 | Early marker; tracks progression |
| Strategy | Approach | Status |
|---|---|---|
| Kinase inhibitors | GSK-3β, CDK5 inhibitors | Preclinical/Phase trials |
| Phosphatase activators | PP2A activators | Preclinical |
| Anti-tau antibodies | Various epitopes | Phase 1/2 trials |
| Tau aggregation inhibitors | Methylene blue, others | Phase 2/3 |
| Tau vaccination | Active immunization | Phase 1/2 |
The study of Phosphorylated Tau Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.