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.

1978Connections

24Hypotheses

12Analyses

50Outgoing

50Incoming

11Experiments

14Debates

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	ARO
Full Name	MAPT-SC Tau ASO Trial (NCT07221344)
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	ARO
Human Protein Atlas	ARO
Associated Diseases	AD, Ad Pathology, Aging, Als, Alzheimer
Known Drugs/Compounds	13G4, berberine, Flavonoids
Interactions	A2M, ACE, ACHE, Actin, AD, AGING
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Glymphatic-Mediated Tau Clearance Dysfunction Excitatory Neuron Synaptic Dysfunction and Mitocho Dual-Circuit Tau Vulnerability Cascade (+18 more)
KG Connections	1976 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 (16)

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 (1158)

Target	Relation	Type	Str
ds-6784494f1741	provides_data_for	dataset	1.00
NEURODEGENERATION	associated_with	gene	1.00
0N3R	encodes	protein	1.00
TAU	associated_with	gene	1.00
DEMENTIA	associated_with	gene	1.00
MICROTUBULE-ASSOCIATED PROTEIN TAU	encodes	protein	0.99
microtubule	binds	process	0.95
Tauopathy	causes	disease	0.95
Alzheimer'S Disease	biomarker_for	disease	0.95
ISG15	upregulates	gene	0.95
Alzheimer Disease	causes	disease	0.95
Neuronal Dysfunction	causes	phenotype	0.95
neuronal degeneration	contributes_to	process	0.95
Tau Hyperphosphorylation	involved_in	process	0.95
tau protein	associated_with	protein	0.95
Amyloid-Beta Toxicity	inhibits	mechanism	0.95
Neuron-Glia Cross-Talk	modulates	process	0.95
Microtubules	interacts_with	process	0.95
Tau protein	associated_with	protein	0.95
Tau Propagation	modulates	process	0.95
Nf-Κb/Nlrp3 Inflammasome Signaling	promotes	pathway	0.95
Microtubule	regulates	protein	0.95
Alzheimer'S Disease	associated_with	disease	0.95
Alzheimer's Disease	associated_with	disease	0.95
Microtubule Stability	inhibits	process	0.95
Microtubule Stabilization	involved_in	process	0.95
Neuroinflammation	associated_with	process	0.95
Microtubule	interacts_with	pathway	0.95
Tau Fibrils	component_of	structure	0.95
Tau Aggregation	involved_in	process	0.95
Microtubule	associated_with	cell_type	0.95
Frontotemporal Dementia	associated_with	disease	0.95
ALZHEIMER	biomarker_for	disease	0.95
Alzheimer Disease	biomarker_for	disease	0.95
tauopathy	associated_with	disease	0.95
Frontotemporal Degeneration	biomarker_for	disease	0.95
Neuronal Development	regulates	process	0.92
4R Tauopathy	involved_in	disease	0.92
Progressive Supranuclear Palsy	biomarker_for	disease	0.92
Labile Domain	regulates	phenotype	0.92
Ad Pathology	associated_with	phenotype	0.92
tauopathies	associated_with	disease	0.91
Microtubules	component_of	cell_type	0.90
TUBULIN	interacts_with	protein	0.90
V337M	associated_with	compound	0.90
Microtubule Stability	regulates	process	0.90
Neurodegeneration	associated_with	process	0.90
MITOCHONDRIAL PROTEINS	interacts_with	protein	0.90
R406W	associated_with	compound	0.90
axonal function	regulates	pathway	0.90

Incoming (820)

Source	Relation	Type	Str
entities-biiib080	associated_with	wiki	0.00
ds-6784494f1741	data_in	dataset	1.00
genes-mapt	documents	wiki_page	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
genes-mapt	describes	wiki_page	1.00
Extracellular Vesicles	transports	biomarker	0.95
CELF2	regulates	protein	0.95
MAPK14	phosphorylates	protein	0.90
ISG15	promotes	gene	0.90
h-23b94ed8	targets	hypothesis	0.90
h-var-69c66a84b3	targets_gene	hypothesis	0.90
h-var-59fc393ba6	targets_gene	hypothesis	0.90
h-var-93e3ef09b3	targets_gene	hypothesis	0.90
h-trem2-6a46fa2c	targets_gene	hypothesis	0.90
h-var-8412ce00a4	targets_gene	hypothesis	0.90
h-var-bc4357c8c5	targets_gene	hypothesis	0.90
h-var-6a0893ffb6	targets_gene	hypothesis	0.90
h-var-f687d4593b	targets_gene	hypothesis	0.90
MARK	phosphorylates	enzyme	0.90
h-var-95b0f9a6bc	targets_gene	hypothesis	0.90
h-var-1906e102cf	targets_gene	hypothesis	0.90
CASEIN KINASE 2	phosphorylates	enzyme	0.90
p38γ	phosphorylates	enzyme	0.90
HLA-A	modulates	gene	0.88
CHMP4B	regulates	protein	0.85
Hdac Inhibitors	downregulates	drug	0.85
autophagy	degrades	process	0.85
PKR	upregulates	entity	0.85
P62	upstream_of	protein	0.85
endolysosomal pathway	regulates	pathway	0.85
Flavonoids	inhibits	compound	0.85
Electroacupuncture	downregulates	drug	0.85
13G4	targets	drug	0.85
Frontotemporal Dementia	associated_with	disease	0.85
phosphorylation	modulates	process	0.85
Tnf-Α	promotes	protein	0.85
AMYLOID	associated_with	gene	0.82
APP	associated_with	gene	0.82
AUTOPHAGY	associated_with	gene	0.82
CDC2	phosphorylates	protein	0.82
IL1B	associated_with	gene	0.80
MIRNAS	targets	gene	0.80
AMYLOID BETA	associated_with	protein	0.80
exosome release	mediates	process	0.80
Metformin	downregulates	drug	0.80
PARKINSON'S DISEASE	associated_with	gene	0.80
ADRA2A	regulates_propagation	gene	0.80
TAU	activates	gene	0.80
lysosomal pathway	degrades	pathway	0.75
endosomal pathway	regulates	pathway	0.75

Targeting Hypotheses (24)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Glymphatic-Mediated Tau Clearance Dysfunction	0.821	neuroscience	Circuit-level neural dynamics in neurode
Excitatory Neuron Synaptic Dysfunction and Mitochondrial Str	0.790	neurodegeneration	Cell type vulnerability debate in Alzhei
Dual-Circuit Tau Vulnerability Cascade	0.754	neuroscience	Circuit-level neural dynamics in neurode
Tau/MAP6 ratio as a master switch for microtubule dynamics p	0.750	neurodegeneration	View
Tau dysfunction destabilizes labile pool	0.750	neurodegeneration	View

Cholinergic Basal Forebrain-Hippocampal Circuit Protection	0.742	neuroscience	Circuit-level neural dynamics in neurode
Tau missorting transitions into an autonomous tau-seeding st	0.740	neurodegeneration	Does tau dendritic missorting persist in
Dopaminergic Ventral Tegmental-Hippocampal Circuit Protectio	0.740	neuroscience	Circuit-level neural dynamics in neurode
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Rece	0.737	neuroscience	Circuit-level neural dynamics in neurode
Microglial Exosome-Mediated Tau Propagation	0.702	neuroscience	Circuit-level neural dynamics in neurode
Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated A	0.696	neuroscience	Circuit-level neural dynamics in neurode
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
Glymphatic-Cholinergic Tau Clearance Cascade	0.666	neuroscience	Circuit-level neural dynamics in neurode
Locus Coeruleus-Hippocampal Circuit Protection	0.653	neuroscience	Circuit-level neural dynamics in neurode
Competition-based domain allocation	0.650	neurodegeneration	View
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
Developmental stage-specific dominance of tau vs MAP6 functi	0.550	neurodegeneration	View
Epigenetic Age Acceleration Moderates the Amyloid-to-Tau Con	0.533	-	Epigenetic clocks as biomarkers for Alzh
REST-like neuronal silencing programs suppress MAPT in sever	0.506	neurodegeneration	Which specific transcription factors med

Mentioning Analyses (12)

Scientific analyses that reference this entity

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.583

Which specific transcription factors mediate MAPT suppression during proteostati

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

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

neurodegeneration | 2026-04-16 | 0 hypotheses

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

neurodegeneration | 2026-04-09 | 0 hypotheses

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

drug discovery | 2026-04-09 | 0 hypotheses

Experiments (11)

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
iPSC-derived astrocyte-neuron co-culture mitochondrial transfer in PD	exploratory	Parkinson's disease	0.900	0.00	iPSC-derived dopaminergic neur	proposed	N/A
Autophagy receptor identification for stress granule elimination	exploratory	neurodegenerative diseases	0.900	0.00	cultured cells under arsenite	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 (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (14)

Multi-agent debates referencing this entity

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

completed · Rounds: 5 · Score: 0.50 · 2026-04-25

Which specific transcription factors mediate MAPT suppression during proteostati

active · Rounds: 4 · Score: 0.66 · 2026-04-25

Can optimized Cas13 guide RNAs selectively silence pathogenic MAPT splice varian

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Is Cas13-based 4R-tau silencing feasible given collateral cleavage risks in post

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

Investigate prion-like spreading of tau pathology through connected brain region

closed · Rounds: 4 · Score: 0.90 · 2026-04-12

While the study shows 53BP1 forms phase-separated foci driven by dilncRNAs, it's

closed · Rounds: 7 · Score: 0.95 · 2026-04-10

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

closed · Rounds: 4 · Score: 0.86 · 2026-04-10

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

closed · Rounds: 4 · Score: 0.95 · 2026-04-10

Sleep disruption as cause and consequence of neurodegeneration

closed · Rounds: 4 · Score: 0.91 · 2026-04-06

Tau propagation mechanisms and therapeutic interception points

closed · Rounds: 3 · Score: 0.95 · 2026-04-04

Related Research

Hypotheses and analyses mentioning MAPT in their description or question text

MAPT

Understanding Entity Pages

Summary

Wiki Pages (16)

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

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

MAPT — Microtubule Associated Protein Tau Gene Entity

ARO-MAPT-SC Tau ASO Trial (NCT07221344)

BIIB080 (MAPTRx)

Pre-Symptomatic Tau Detection in MAPT Mutation Carriers

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

MAPT - Microtubule-Associated Protein Tau

MAPT Protein

MAPT-Mutant Neurons

MAPT Haplotypes (H1/H2)

MAPT Mutation Penetrance and Phenotypic Modifiers in Tauopathies

Pathway Diagram

Outgoing (1158)

Incoming (820)

Targeting Hypotheses (24)

Mentioning Analyses (12)

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Which specific transcription factors mediate MAPT suppression during proteostati

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

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

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

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

Sleep disruption as cause and consequence of neurodegeneration

Experiments (11)

Related Papers (0)

Debates (14)

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Which specific transcription factors mediate MAPT suppression during proteostati

Can optimized Cas13 guide RNAs selectively silence pathogenic MAPT splice varian

Is Cas13-based 4R-tau silencing feasible given collateral cleavage risks in post

Investigate prion-like spreading of tau pathology through connected brain region

While the study shows 53BP1 forms phase-separated foci driven by dilncRNAs, it's

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

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

Sleep disruption as cause and consequence of neurodegeneration

Tau propagation mechanisms and therapeutic interception points

Related Research

Cholinergic Basal Forebrain-Hippocampal Circuit Protection

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

Dopaminergic Ventral Tegmental-Hippocampal Circuit Protection

Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor Impairment

Microglial Exosome-Mediated Tau Propagation

Dual-Circuit Tau Vulnerability Cascade with Glial-Mediated Amplification

Selective Tau Kinase Inhibition in Vulnerable Neuronal Subtypes

Microglial TREM2-Mediated Tau Phagocytosis Impairment

Glymphatic-Cholinergic Tau Clearance Cascade

Locus Coeruleus-Hippocampal Circuit Protection

Competition-based domain allocation

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

Rutin reduces ROS- and metal-driven tau oligomer nucleation