ID: h-c976c89516
Hypothesis
Astrocyte-Neuron Lactate Shuttle via SST-Mediated Metabolic Coupling (Deprioritize)
tFUS-activated EC-II SST interneurons trigger astrocytic Ca²⁺ waves via ATP release, stimulating glycolysis and lactate provision to EC-III pyramidal neurons, restoring their gamma generation capacity.
🧬 MCT1, MCT4 (astrocytic lactate transporters); Pannexin-1; KATP channels🩺 alzheimers🎯 Composite 35%💱 $0.47▲23.9%proposed
Alzheimer's disease
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
tFUS-activated EC-II SST interneurons trigger astrocytic Ca²⁺ waves via ATP release, stimulating glycolysis and lactate provision to EC-III pyramidal neurons, restoring their gamma generation capacity. Too indirect with too many unvalidated intermediate steps (SST→ATP→astrocyte Ca²⁺→glycolysis→lactate→EC-III neurons). ANLS hypothesis itself is controversial. No clear intervention lever.
🧬 Mechanism
🔗 Mechanism from KG for MCT1, MCT4 (astrocytic lactate transporters); Pannexin-1; KATP channels
Auto-built from this analysis's top knowledge-graph edges.
graph TD
gamma_entrainment["gamma entrainment"] -.->|inhibits| Amyloid_Plaque_Burden["Amyloid Plaque Burden"]
n40_Hz_gamma_entrainment["40 Hz gamma entrainment"] -.->|inhibits| Amyloid_Plaque_Burden_1["Amyloid Plaque Burden"]
theta_gamma_coupling["theta-gamma coupling"] -->|associated with| memory_consolidation["memory consolidation"]
BDNF["BDNF"] -->|regulates| excitatory_synapse_mainte["excitatory synapse maintenance"]
perforant_path_degenerati["perforant path degeneration"] -->|causes| Memory_Deficits["Memory Deficits"]
SST_interneurons["SST_interneurons"] -->|associated with| microglial_inflammation["microglial inflammation"]
SST["SST"] -->|regulates| microglial_inflammation_2["microglial inflammation"]
n40_Hz_tACS["40 Hz tACS"] -->|regulates| Cognitive_function["Cognitive function"]
neuroinflammatory_biomark["neuroinflammatory biomarkers"] -->|associated with| Ad_Pathology["Ad Pathology"]
perforant_path_degenerati_3["perforant path degeneration"] -->|associated with| Memory_Deficits_4["Memory Deficits"]
n40_Hz_stimulation["40 Hz stimulation"] -->|regulates| Cognitive_function_5["Cognitive function"]
network_hyperexcitability["network hyperexcitability"] -->|causes| Alzheimer_s_disease["Alzheimer's_disease"]
style gamma_entrainment fill:#4fc3f7,stroke:#333,color:#000
style Amyloid_Plaque_Burden fill:#4fc3f7,stroke:#333,color:#000
style n40_Hz_gamma_entrainment fill:#4fc3f7,stroke:#333,color:#000
style Amyloid_Plaque_Burden_1 fill:#4fc3f7,stroke:#333,color:#000
style theta_gamma_coupling fill:#4fc3f7,stroke:#333,color:#000
style memory_consolidation fill:#4fc3f7,stroke:#333,color:#000
style BDNF fill:#ce93d8,stroke:#333,color:#000
style excitatory_synapse_mainte fill:#4fc3f7,stroke:#333,color:#000
style perforant_path_degenerati fill:#4fc3f7,stroke:#333,color:#000
style Memory_Deficits fill:#4fc3f7,stroke:#333,color:#000
style SST_interneurons fill:#4fc3f7,stroke:#333,color:#000
style microglial_inflammation fill:#4fc3f7,stroke:#333,color:#000
style SST fill:#ce93d8,stroke:#333,color:#000
style microglial_inflammation_2 fill:#4fc3f7,stroke:#333,color:#000
style n40_Hz_tACS fill:#ce93d8,stroke:#333,color:#000
style Cognitive_function fill:#4fc3f7,stroke:#333,color:#000
style neuroinflammatory_biomark fill:#ce93d8,stroke:#333,color:#000
style Ad_Pathology fill:#ce93d8,stroke:#333,color:#000
style perforant_path_degenerati_3 fill:#4fc3f7,stroke:#333,color:#000
style Memory_Deficits_4 fill:#4fc3f7,stroke:#333,color:#000
style n40_Hz_stimulation fill:#4fc3f7,stroke:#333,color:#000
style Cognitive_function_5 fill:#4fc3f7,stroke:#333,color:#000
style network_hyperexcitability fill:#4fc3f7,stroke:#333,color:#000
style Alzheimer_s_disease fill:#ef5350,stroke:#333,color:#000⚖️ Evidence
⚖️ Evidence Matrix3 supports3 contradicts
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — MCT1
No curated PDB or AlphaFold mapping for MCT1 yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
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 MCT1, MCT4 (astrocytic lactate transporters); Pannexin-1; KATP channels.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
↗
Rising
7d Momentum
▲ 1.1%
Volatility
Low
0.0038
Events (7d)
3
Price History
▲23.9%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesizer
| source | v1_phase_c_backfill |
| origin_type | debate_synthesizer |
| _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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