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.
Overview
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.
Phosphorylation Biology
Normal Tau Phosphorylation
Tau is normally phosphorylated at low levels (~2-3 mol phosphate/mol tau)
Phosphorylation regulates tau's ability to bind microtubules and modulate axonal transport
Tau PET ligands: Flortaucipir (AV-1451), MK-6240, PI-2620
Correlation: Tau PET signal correlates with cognitive impairment
Therapeutic Implications
Anti-tau Therapies
Key Publications
[Tau phosphorylation in AD](https://doi.org/10.1016/j.tcb.2020.01.003) - W. Mandelkow, 2020
[Tau prion-like spreading](https://doi.org/10.1016/j.cell.2019.02.035) - M. Goedert, 2019
[p-tau181 as AD biomarker](https://doi.org/10.1001/jamaneurol.2019.2215) - K. Blennow, 2019
[Tau PET imaging](https://doi.org/10.1038/nrneurol.2017.120) - M. Villemagne, 2018
Background
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.
See Also
[MAPT Gene](/genes/mapt) - Gene encoding tau protein
[Tau Protein](/proteins/tau) - Full-length tau protein
[Mandelkow EW, Mandelkow E, Tau in physiology and pathology (2010)](https://doi.org/10.1038/nrn3024)
[Goedert M, Eisenberg DS, Crowther RA, Propagation of Tau aggregates and neurodegeneration (2017)](https://doi.org/10.1146/annurev-neuro-072116-031153)
[Blennow K, Zetterberg H, Biomarkers for Alzheimer's disease: current status and prospects (2021)](https://doi.org/10.1002/wps.20824)
[Scheltens P, De Strooper B, Kivipelto M, et al, Alzheimer's disease (2021)](https://doi.org/10.1016/S0140-6736(20)
[Hampel H, Blennow K, Shaw LM, Zetterberg H, Biomarkers for Alzheimer's disease: current status and prospects (2023)](https://doi.org/10.1038/s41380-022-01786-2)
[Villemagne VL, Dore V, Burnham SC, Masters CL, Rowe CC, Imaging tau and amyloid-beta proteinopathies in Alzheimer disease and other dementias (2018)](https://doi.org/10.1016/S1474-4422(18)
[Xia Y, de Strooper B, Tau in Alzheimer's disease: mechanisms and therapeutic strategies (2022)](https://doi.org/10.1007/s12031-022-02054-4)
[Morris M, Maeda S, Mucke L, The many faces of tau (2011)](https://doi.org/10.1016/j.neuron.2011.04.009)
[Johnson KA, Schultz A, Betensky RA, et al, Tau PET imaging in aging and Alzheimer's disease (2016)](https://doi.org/10.1001/jamaneurol.2016.2018)
[Pascoal TA, Benedet AL, Tudorascu DR, et al, Longitudinal changes in tau PET across the cognitive spectrum (2021)](https://doi.org/10.1212/WNL.0000000000011526)