MAPT

Understanding Entity Pages

This page aggregates everything SciDEX knows about MAPT: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

Summary

Microtubule-Associated Protein Tau (MAPT) encodes the tau protein, essential for microtubule stabilization, axonal transport, and neuronal morphology. Alternative splicing produces six tau isoforms (0N3R to 2N4R) in the adult human brain. Hyperphosphorylated tau detaches from microtubules, forming paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) that are pathological hallmarks of AD and other tauopathies. MAPT mutations cause frontotemporal dementia with parkinsonism (FTDP-17). The H1 haplotype of MAPT is associated with progressive supranuclear palsy and corticobasal degeneration. Tau pathology spreads trans-synaptically in a prion-like manner, and tau burden correlates more closely with cognitive decline than amyloid plaques, making tau a prime therapeutic target.

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flowchart TD
    MAPT_gene["MAPT Gene"]
    TAU_protein["TAU Protein"]
    tau_pathology["Tau Pathology<br/>(Hyperphosphorylation)"]
    neurofibrillary_tangles["Neurofibrillary<br/>Tangles"]
    lysosomal_dysfunction["Lysosomal<br/>Dysfunction"]
    neurodegeneration["Neurodegeneration"]
    alzheimers["Alzheimer's<br/>Disease"]
    
    GSK3B["GSK-3beta<br/>(Kinase)"]
    APOE4["APOE4<br/>(Risk Factor)"]
    NBR1["NBR1<br/>(Autophagy Receptor)"]
    SQSTM1["SQSTM1/p62<br/>(Autophagy Adaptor)"]
    BAG3["BAG3<br/>(Chaperone Co-factor)"]
    
    microtubule_binding["Microtubule<br/>Binding"]
    axonal_transport["Axonal<br/>Transport"]
    autophagy["Autophagy<br/>Clearance"]
    
    MAPT_gene --|"encodes"|--> TAU_protein
    TAU_protein --|"normal function"|--> microtubule_binding
    microtubule_binding --|"maintains"|--> axonal_transport
    
    GSK3B --|"phosphorylates"|--> TAU_protein
    APOE4 --|"modulates"|--> TAU_protein
    TAU_protein --|"abnormal"|--> tau_pathology
    tau_pathology --|"forms"|--> neurofibrillary_tangles
    
    NBR1 --|"regulates"|--> TAU_protein
    SQSTM1 --|"targets for degradation"|--> TAU_protein
    BAG3 --|"assists clearance"|--> TAU_protein
    NBR1 --|"promotes"|--> autophagy
    SQSTM1 --|"promotes"|--> autophagy
    autophagy --|"clears"|--> TAU_protein
    
    tau_pathology --|"causes"|--> lysosomal_dysfunction
    neurofibrillary_tangles --|"leads to"|--> neurodegeneration
    lysosomal_dysfunction --|"contributes to"|--> neurodegeneration
    neurodegeneration --|"manifests as"|--> alzheimers
    
    style MAPT_gene fill:#006494
    style TAU_protein fill:#006494
    style GSK3B fill:#4a1a6b
    style APOE4 fill:#4a1a6b
    style NBR1 fill:#1b5e20
    style SQSTM1 fill:#1b5e20
    style BAG3 fill:#1b5e20
    style autophagy fill:#1b5e20
    style tau_pathology fill:#ef5350
    style neurofibrillary_tangles fill:#ef5350
    style lysosomal_dysfunction fill:#ef5350
    style neurodegeneration fill:#5d4400
    style alzheimers fill:#5d4400