gene

MAPT

Entity Detail — Knowledge Graph Node

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.

2026Connections

30Hypotheses

23Analyses

50Outgoing

50Incoming

9Experiments

20Debates

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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🧬 Gene Info

Gene Symbol	MAPT
Full Name	Microtubule-Associated Protein Tau
Aliases	H1/H2
Chromosome	17q21.31
Protein Type	Structural Protein
Target Class	Structural Protein
Function	Tau aggregation inhibitors, anti-tau antibodies, tau phosphorylation modulators
Mechanism of Action	Tau aggregation inhibitors, anti-tau antibodies, tau phosphorylation modulators
Druggability	Medium (0.45)
Clinical Stage	Phase III
Molecular Weight	65 kDa
Amino Acids	441 aa
Exons	16
Pathways	Amyloid, Apoptosis, Autophagy, Camp Signaling, Cholesterol
UniProt ID	A0A7I2PJZ2
GeneCards	MAPT
Human Protein Atlas	MAPT
Associated Diseases	AD, Ad Pathology, Aging, Als, Alzheimer
Known Drugs/Compounds	13G4, anti-tau antibodies, berberine, Flavonoids, HSP90 inhibitors, Rutin
Interactions	A2M, ACE, ACHE, Actin, AD, AGING
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Microglial-Mediated Tau Clearance Dysfunction via Glymphatic-Mediated Tau Clearance Dysfunction MAPT tau seeding and release across AD, FTD, and P (+40 more)
KG Connections	2023 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — MAPT Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

5O3L — X-ray / Cryo-EM

🔮 AI Predicted Structure

P10636 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (17)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    MAPT_gene["MAPT Gene"]
    TAU_protein["TAU Protein"]
    tau_pathology["Tau Pathology
(Hyperphosphorylation)"]
    neurofibrillary_tangles["Neurofibrillary
Tangles"]
    lysosomal_dysfunction["Lysosomal
Dysfunction"]
    neurodegeneration["Neurodegeneration"]
    alzheimers["Alzheimer's
Disease"]
    
    GSK3B["GSK-3beta
(Kinase)"]
    APOE4["APOE4
(Risk Factor)"]
    NBR1["NBR1
(Autophagy Receptor)"]
    SQSTM1["SQSTM1/p62
(Autophagy Adaptor)"]
    BAG3["BAG3
(Chaperone Co-factor)"]
    
    microtubule_binding["Microtubule
Binding"]
    axonal_transport["Axonal
Transport"]
    autophagy["Autophagy
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

Outgoing (1189)

Target	Relation	Type	Str
MAPT	encodes	protein	0.00
TAU	associated_with	gene	1.00
ds-6784494f1741	provides_data_for	dataset	1.00
DEMENTIA	associated_with	gene	1.00
0N3R	encodes	protein	1.00
NEURODEGENERATION	associated_with	gene	1.00
MICROTUBULE-ASSOCIATED PROTEIN TAU	encodes	protein	0.99
Amyloid-Beta Toxicity	inhibits	mechanism	0.95
Alzheimer's Disease	associated_with	disease	0.95
tauopathy	associated_with	disease	0.95
Microtubule	associated_with	cell_type	0.95
Microtubules	interacts_with	process	0.95
Frontotemporal Dementia	associated_with	disease	0.95
Alzheimer'S Disease	associated_with	disease	0.95
Tau Hyperphosphorylation	involved_in	process	0.95
Tau Propagation	modulates	process	0.95
Alzheimer'S Disease	biomarker_for	disease	0.95
Neuronal Dysfunction	causes	phenotype	0.95
Alzheimer Disease	causes	disease	0.95
Tauopathy	causes	disease	0.95
Tau Aggregation	involved_in	process	0.95
microtubule	binds	process	0.95
neuronal degeneration	contributes_to	process	0.95
Alzheimer Disease	biomarker_for	disease	0.95
tau protein	associated_with	protein	0.95
Frontotemporal Degeneration	biomarker_for	disease	0.95
Microtubule	regulates	protein	0.95
Nf-Κb/Nlrp3 Inflammasome Signaling	promotes	pathway	0.95
Microtubule Stability	inhibits	process	0.95
Neuroinflammation	associated_with	process	0.95
ALZHEIMER	biomarker_for	disease	0.95
Neuron-Glia Cross-Talk	modulates	process	0.95
ISG15	upregulates	gene	0.95
Tau Fibrils	component_of	structure	0.95
Microtubule Stabilization	involved_in	process	0.95
Tau protein	associated_with	protein	0.95
Microtubule	interacts_with	pathway	0.95
Neuronal Development	regulates	process	0.92
4R Tauopathy	involved_in	disease	0.92
Labile Domain	regulates	phenotype	0.92
Progressive Supranuclear Palsy	biomarker_for	disease	0.92
Ad Pathology	associated_with	phenotype	0.92
tauopathies	associated_with	disease	0.91
Axon Microtubule Organization	involved_in	process	0.90
labile microtubule domain	associated_with	phenotype	0.90
Alzheimer Disease	associated_with	disease	0.90
Axon	expressed_in	cell_type	0.90
Axonal Microtubule Stability	modulates	phenotype	0.90
Disease Severity	correlates_with	phenotype	0.90
axonal function	regulates	pathway	0.90

Incoming (837)

Source	Relation	Type	Str
entities-biiib080	associated_with	wiki	0.00
MAPT	encodes	gene	0.00
ds-6784494f1741	data_in	dataset	1.00
genes-mapt	describes	wiki	1.00
genes-mapt	documents	wiki	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
CELF2	regulates	protein	0.95
Extracellular Vesicles	transports	biomarker	0.95
MAPK14	phosphorylates	protein	0.90
MARK	phosphorylates	enzyme	0.90
p38γ	phosphorylates	enzyme	0.90
ISG15	promotes	gene	0.90
h-var-6a0893ffb6	targets_gene	hypothesis	0.90
h-var-f687d4593b	targets_gene	hypothesis	0.90
CASEIN KINASE 2	phosphorylates	enzyme	0.90
h-var-8412ce00a4	targets_gene	hypothesis	0.90
h-var-95b0f9a6bc	targets_gene	hypothesis	0.90
h-trem2-6a46fa2c	targets_gene	hypothesis	0.90
h-var-69c66a84b3	targets_gene	hypothesis	0.90
h-23b94ed8	targets	hypothesis	0.90
h-var-59fc393ba6	targets_gene	hypothesis	0.90
h-var-bc4357c8c5	targets_gene	hypothesis	0.90
h-var-1906e102cf	targets_gene	hypothesis	0.90
h-var-93e3ef09b3	targets_gene	hypothesis	0.90
anti-tau antibodies	targets	drug	0.90
tau ASO BIIB080	targets	drug	0.90
HLA-A	modulates	gene	0.88
endolysosomal pathway	regulates	pathway	0.85
Hdac Inhibitors	downregulates	drug	0.85
Flavonoids	inhibits	compound	0.85
13G4	targets	drug	0.85
APOE	modulates_phosphorylation	gene	0.85
PKR	upregulates	entity	0.85
Frontotemporal Dementia	associated_with	disease	0.85
CHMP4B	regulates	protein	0.85
autophagy	degrades	process	0.85
phosphorylation	modulates	process	0.85
P62	upstream_of	protein	0.85
Electroacupuncture	downregulates	drug	0.85
Tnf-Α	promotes	protein	0.85
AUTOPHAGY	associated_with	gene	0.82
h-cross-synth-mapt-tau-seeding	proposes_shared_mechanism	hypothesis	0.82
AMYLOID	associated_with	gene	0.82
CDC2	phosphorylates	protein	0.82
APP	associated_with	gene	0.82
AMYLOID BETA	associated_with	protein	0.80
IL1B	associated_with	gene	0.80
MIRNAS	targets	gene	0.80
Metformin	downregulates	drug	0.80
exosome release	mediates	process	0.80

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Rece	0.937	neuroscience	Circuit-level neural dynamics in neurode
Glymphatic-Mediated Tau Clearance Dysfunction	0.865	neuroscience	Proteomics Differential Expression in AD
MAPT tau seeding and release across AD, FTD, and PD-spectrum	0.812	multi	Cross-disease neurodegeneration mechanis
Dual-Circuit Tau Vulnerability Cascade	0.774	neuroscience	Circuit-level neural dynamics in neurode
Cholinergic Basal Forebrain-Hippocampal Circuit Protection	0.760	neuroscience	Circuit-level neural dynamics in neurode

Repeat-domain exposure defines seed-competent tau conformers	0.760	neurodegeneration	Seed-competent tau conformers in trans-s
Dopaminergic Ventral Tegmental-Hippocampal Circuit Protectio	0.751	neuroscience	Circuit-level neural dynamics in neurode
Tau/MAP6 ratio as a master switch for microtubule dynamics p	0.750	neurodegeneration	-
Tau dysfunction destabilizes labile pool	0.750	neurodegeneration	-
Tau missorting transitions into an autonomous tau-seeding st	0.740	neurodegeneration	Does tau dendritic missorting persist in
A tau PTM barcode gates trans-synaptic templating	0.738	neurodegeneration	Seed-competent tau conformers in trans-s
Selective Tau Kinase Inhibition in Vulnerable Neuronal Subty	0.676	neurodegeneration	Cell type vulnerability in Alzheimers Di
Microglial TREM2-Mediated Tau Phagocytosis Impairment	0.676	neuroscience	Circuit-level neural dynamics in neurode
Locus Coeruleus-Hippocampal Circuit Protection	0.668	neuroscience	Circuit-level neural dynamics in neurode
Glymphatic-Cholinergic Tau Clearance Cascade	0.666	neuroscience	Circuit-level neural dynamics in neurode
Excitatory Neuron Synaptic Dysfunction and Mitochondrial Str	0.660	neurodegeneration	Cell type vulnerability debate in Alzhei
Competition-based domain allocation	0.650	neurodegeneration	-
Rutin stabilizes a non-nucleating tau conformer through dire	0.627	neurodegeneration	What is the molecular mechanism by which
ATF4-DDIT3 stress signaling indirectly represses MAPT transc	0.624	neurodegeneration	Which specific transcription factors med
Tau Cross-Seeding and Interaction	0.610	neurodegeneration	What mechanisms underlie TDP-43's contri
Rutin reduces ROS- and metal-driven tau oligomer nucleation	0.602	neurodegeneration	What is the molecular mechanism by which
HSF1 reprioritizes transcription and suppresses MAPT while r	0.598	neurodegeneration	Which specific transcription factors med
Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated A	0.568	neuroscience	Circuit-level neural dynamics in neurode
Developmental stage-specific dominance of tau vs MAP6 functi	0.550	neurodegeneration	-
Microglial Exosome-Mediated Tau Propagation	0.539	neuroscience	Circuit-level neural dynamics in neurode
REST-like neuronal silencing programs suppress MAPT in sever	0.506	neurodegeneration	Which specific transcription factors med
Glymphatic-Mediated Tau Clearance Dysfunction (Proteomics DE	0.500	alzheimers	-
Combinatorial PTM signatures distinguish pathological from p	0.455	neurodegeneration	Which specific post-translational modifi
Tau Conformational Change-Triggered Membrane Disruption	0.455	molecular-biology	Can nanobodies achieve selective membran
pH-Activated Membrane Fusion Nanobodies	0.455	molecular-biology	Can nanobodies achieve selective membran

Mentioning Analyses (23)

Scientific analyses that reference this entity

Cross-disease neurodegeneration mechanism synthesis

neurodegeneration | 2026-04-28 | 17 hypotheses Top: 0.828

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.585

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.387

Which specific transcription factors mediate MAPT suppression during proteostati

neurodegeneration | 2026-04-25 | 3 hypotheses Top: 0.624

What is the molecular mechanism by which rutin inhibits tau aggregation and olig

neurodegeneration | 2026-04-25 | 3 hypotheses Top: 0.627

Experiments (9)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Plasma ATN biomarkers across AD continuum in Chilean cohort	clinical	Alzheimer's disease	0.950	0.00	Chilean older adults (n=318) w	proposed	N/A
Tau depletion effects on neuronal development in primary cultures	exploratory		0.900	0.00	primary rodent neuronal cultur	proposed	N/A
Differential GWAS of schizophrenia vs PTSD	exploratory	schizophrenia, post-traumatic	0.900	0.00	human patients - European ance	proposed	N/A
Tau depletion effects on neuronal development in primary cultures	exploratory		0.900	0.00	primary rodent neuronal cultur	proposed	N/A
Creation and validation of 3xAD-ChAT-Cre mouse model	validation	Alzheimer's disease	0.900	0.00	3xAD-ChAT-Cre transgenic mice	proposed	N/A
GTEx brain tissue expression analysis of MAPT/CRHR1 locus	exploratory	schizophrenia, post-traumatic	0.850	0.00	human brain tissue samples fro	proposed	N/A
Microtubule domain analysis in adult axons	exploratory		0.800	0.00	adult rodent axons	proposed	N/A
Tau depletion effects on microtubule domains in adult axons	exploratory		0.800	0.00	adult rodent neurons	proposed	N/A
Pre-Symptomatic Tau Detection in MAPT Mutation Carriers	clinical	ALS	0.400	0.50	human	proposed	$6,550,000

Related Papers (8)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Mapping the Brain's Glymphatic System. [PMID:41751308]	Voumvourakis K, Thomaidis NS, Tsiodras S	Biomedicines	2026
Melatonin Mitigates Sleep Restriction-Induced Cognitive and Glymphatic Dysfuncti [PMID:40293704]	Sun H, Cao Q, He X, Du X, Jiang X, Wu T,	Molecular neurobiology	2025
Clearance mechanisms of the glymphatic/lymphatic system in the brain: new therap [PMID:41376656]	He Z, Sun J	Cognitive neurodynamics	2025
Glymphatic and meningeal lymphatic dysfunction in Alzheimer's disease: Mechanism [PMID:41152198]	Ding J, Zhao C, Hao X, Jiao H	Alzheimer's & dementia : the j	2025
When sleep fails, brain clearance suffers: the role of glymphatic impairment in [PMID:41315137]	["De la Herr\u00e1n-Arita Alberto K"]	Acta neurologica Belgica	2025
LRRK2 Promotes Tau Accumulation, Aggregation and Release. [PMID:26014385]	Unknown	Molecular neurobiology	2017
Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and A [PMID:18322368]	Unknown	Neuro-degenerative diseases	2008
The role of tau (MAPT) in frontotemporal dementia and related tauopathies. [PMID:15365985]	Unknown	Human mutation	2005

Debates (20)

Multi-agent debates referencing this entity

Second debate: Microglial TREM2-SYK Pathway Enhancement

closed · Rounds: 4 · Score: 0.57 · 2026-04-28

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

closed · Rounds: 4 · Score: 0.72 · 2026-04-28

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

closed · Rounds: 4 · Score: 0.65 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

closed · Rounds: 4 · Score: 0.71 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

closed · Rounds: 4 · Score: 0.87 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

closed · Rounds: 4 · Score: 0.48 · 2026-04-27

Debate: LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Primin

closed · Rounds: 4 · Score: 0.12 · 2026-04-27

Debate: ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE P

closed · Rounds: 4 · Score: 0.42 · 2026-04-27

Related Research

Hypotheses and analyses mentioning MAPT in their description or question text

MAPT

Understanding Entity Pages

Summary

Wiki Pages (17)

MAPT - Microtubule-Associated Protein Tau

BIIB080 (MAPTRx) Antisense Oligonucleotide for Alzheimer's Disease

MAPT→Tau→Aggregation→PSP Causal Chain

BIIB080 (MAPTRx)

Tau-MAPT-Tubulin Assembly

BIIB080 (MAPTRx) ASO Therapy for PSP

ARO-MAPT-SC Tau ASO Trial (NCT07221344) - Arrowhead Pharmaceuticals

MAPT — Microtubule Associated Protein Tau Gene Entity

ARO-MAPT-SC Tau ASO Trial (NCT07221344)

BIIB080 (MAPTRx)

Pre-Symptomatic Tau Detection in MAPT Mutation Carriers

Validated Hypothesis: MAPT tau seeding and release across AD, FTD, and PD-spectrum disease

TDP-43 vs Tau Pathology Determination in GRN vs MAPT Mutation Carriers

MAPT Protein

MAPT-Mutant Neurons

MAPT Haplotypes (H1/H2)

MAPT Mutation Penetrance and Phenotypic Modifiers in Tauopathies

Pathway Diagram

Outgoing (1189)

Incoming (837)

Targeting Hypotheses (30)

Mentioning Analyses (23)

Cross-disease neurodegeneration mechanism synthesis

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Which specific transcription factors mediate MAPT suppression during proteostati

What is the molecular mechanism by which rutin inhibits tau aggregation and olig

Cas13 gRNA Design for Silencing MAPT (Tau) Transcripts in Alzheimer's Disease

Multi-modal Biomarker Panel Design for Early AD Detection

Why have anti-Aβ clinical trials failed despite the established role of Aβ in AD

What is the atomic-resolution structure of K280-acetylated tau and how does it t

Extracellular vesicle biomarkers for early AD detection

Do tau aggregates represent protective responses or primary pathogenic drivers i

Do tau-containing vesicles exhibit unique surface glycosylation patterns that di

What are the minimal structural requirements for HSP70/HSP90 inhibitors to achie

How can ESCRT or SNARE targeting achieve tau-specific effects without disrupting

What determines the specificity of DDR protein recruitment to dilncRNA-induced c

Tau propagation mechanisms and therapeutic interception points

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Circuit-level neural dynamics in neurodegeneration

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Cell type vulnerability debate in Alzheimer's disease (SEA-AD v4)

Tau propagation mechanisms and therapeutic interception points

Sleep disruption as cause and consequence of neurodegeneration

Experiments (9)

Related Papers (8)

Debates (20)

Second debate: Microglial TREM2-SYK Pathway Enhancement

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

Debate: LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Primin

Debate: ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE P

Related Research

Repeat-domain exposure defines seed-competent tau conformers

Dopaminergic Ventral Tegmental-Hippocampal Circuit Protection

Tau missorting transitions into an autonomous tau-seeding state after transient

A tau PTM barcode gates trans-synaptic templating

Selective Tau Kinase Inhibition in Vulnerable Neuronal Subtypes

Microglial TREM2-Mediated Tau Phagocytosis Impairment

Locus Coeruleus-Hippocampal Circuit Protection

Glymphatic-Cholinergic Tau Clearance Cascade

Excitatory Neuron Synaptic Dysfunction and Mitochondrial Stress via MAPT (tau)

Rutin stabilizes a non-nucleating tau conformer through direct MAPT repeat-domai

ATF4-DDIT3 stress signaling indirectly represses MAPT transcription during prote

Tau Cross-Seeding and Interaction