ID: h-a0b246fc70da
Hypothesis
Tau/MAP6 antagonism in neurodegeneration progression
In tauopathies, pathological tau alterations may disrupt the antagonistic balance with MAP6, causing excessive stabilization and loss of adaptive plasticity, while in other conditions the relationship may be shifted toward excess lability.
EvidenceStrong (60%)📖 6 cit🗣 1 debates✓ 6 support✗ 2 oppose
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🧪 Overview
In tauopathies, pathological tau alterations may disrupt the antagonistic balance with MAP6, causing excessive stabilization and loss of adaptive plasticity, while in other conditions the relationship may be shifted toward excess lability
Prediction: MAP6 expression levels or post-translational modifications will be altered in tauopathy patient samples as a compensatory response to tau dysfunction
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["MAPT/Tau Occupancy<br/>Dynamic Microtubule Binding"]
B["MAP6 Occupancy<br/>Cold-Stable Domain Support"]
C["Shared Microtubule Lattice<br/>Domain Allocation Competition"]
D["GSK3B/CRMP2 Cue Integration<br/>Plasticity Signaling"]
E["Axonal Remodeling Balance<br/>Stable vs Labile Segments"]
F["Transport and Branching<br/>Adaptive Circuit Plasticity"]
G["Tau-MAP6 Imbalance<br/>Rigid or Unstable Cytoskeleton"]
A --> C
B --> C
C --> D
D --> E
E --> F
G -.->|"disrupts"| C
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#81c784,color:#81c784
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix6 supports2 contradicts
Supports
In tauopathies, pathological tau alterations may disrupt the antagonistic balance with MAP6, causing excessive stabilization and loss of adaptive plasticity, while in other conditions the relationship may be shifted toward excess lability
Supports
The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes.
Supports
ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule-associated proteins.
Supports
Microtubules (tau) as an emerging therapeutic target: NAP (davunetide).
Contradicts
Tau/MAP6 antagonism is shown in neuronal development models, but this does not establish that the same balance drives adult neurodegeneration progression or treatment response.
Contradicts
A microtubule-stabilizing peptide strategy failed to show clinical benefit in progressive supranuclear palsy, cautioning against simple cytoskeletal-stabilization translation in tauopathy.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — MAP6
No curated PDB or AlphaFold mapping for MAP6 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for MAP6 from GTEx v10.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for MAP6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▼ 0.3%
Volatility
High
0.0822
Events (7d)
2
Price History
▼3.0%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF MAP6 post-translational modifications (acetylation, phosphorylation) are compared across post-mortem prefrontal cortex samples from early-stage Alzheimer's disease (Braak III-IV) versus advanced di | Higher MAP6 acetylation in early AD (≤50% increase) and lower MAP6 acetylation in late AD (≥30% decrease) relative to age-matched controls | — no observation — | pending | 0.55 |
| IF MAP6 expression is genetically increased via viral vector delivery in pre-symptomatic P301S tau transgenic mice (a model of frontotemporal dementia), THEN dendritic spine density in hippocampal CA1 | Increased spine density (25% or greater) and enhanced synaptic plasticity markers in hippocampus of MAP6-overexpressing P301S mice | — no observation — | pending | 0.65 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF MAP6 expression is genetically increased via viral vector delivery in pre-symptomatic P301S tau transgenic mice (a model of frontotemporal dementia), THEN dendritic spine density in hippocampal CA1 neurons will increase by at least 25% compared to GFP-transduced controls within 6 weeks of injecti
Predicted outcome: Increased spine density (25% or greater) and enhanced synaptic plasticity markers in hippocampus of MAP6-overexpressing P301S mice
Falsification: No significant change or decrease in spine density/synaptic markers despite successful MAP6 overexpression (confirmed by western blot showing ≥2-fold elevation)
pendingconf 55%
IF MAP6 post-translational modifications (acetylation, phosphorylation) are compared across post-mortem prefrontal cortex samples from early-stage Alzheimer's disease (Braak III-IV) versus advanced disease (Braak V-VI), THEN acetylated MAP6 will be significantly elevated in early-stage samples as a
Predicted outcome: Higher MAP6 acetylation in early AD (≤50% increase) and lower MAP6 acetylation in late AD (≥30% decrease) relative to age-matched controls
Falsification: No significant difference in MAP6 PTMs between AD stages or control samples, or a monotonic increase/decrease across all stages
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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