ID: h-3294f3a8
Hypothesis
CCR2+ Monocyte Depletion as Restoration of CNS Immune Privilege
CCR2+ Monocyte Depletion as Restoration of CNS Immune Privilege.
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 4 support✗ 4 oppose
🧪 Overview
CCR2+ Monocyte Depletion as Restoration of CNS Immune Privilege
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["CCL2/MCP-1 Gradient<br/>Blood-Brain Barrier Chemokine Field"]
B["CCR2+ Monocyte Recruitment<br/>Peripheral Immune Cell Extravasation"]
C["Microglial Activation Bias<br/>M1 Pro-inflammatory State Shift"]
D["Pro-inflammatory Cytokine Storm<br/>IL1B, TNF-alpha, IL6 Amplification"]
E["Synaptic Pruning Dysregulation<br/>Excess or Insufficient Phagocytosis"]
F["Neuronal Loss and Network Dysfunction<br/>Cognitive Decline Substrate"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix4 supports4 contradicts
Supports
Adoptive transfer of CCR2+ monocytes restores cognitive deficits in CCR2-KO mice
Contradicts
CCR2+ monocytes contribute to Aβ clearance in early disease; depletion worsens amyloid pathology in APP/PS1 mice at early timepoints
Contradicts
Natalizumab (anti-α4 integrin) showed neurological worsening in AD patients
Contradicts
Single-cell RNA-seq studies suggest human AD microglia are predominantly self-renewing with minimal monocyte contribution
Contradicts
Species differences: Mouse models show more robust monocyte infiltration across BBB compared to humans where BBB remains largely intact until late stages
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — CCL2
No curated PDB or AlphaFold mapping for CCL2 yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for CCL2/CCR2 axis; specifically CCR2+ monocytes from GTEx v10.
💉 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 CCL2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
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🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF CCR2+ monocytes are selectively depleted using CCR2-DTR bone marrow chimeric mice before EAE induction (via DT administration at 10 μg/g for 3 consecutive days), THEN clinical EAE scores will decre | EAE clinical score reduction of ≥40% and CNS CD45+ cell count reduction of ≥50% | — no observation — | pending | 0.65 |
| IF anti-CCR2 monoclonal antibody (clone MC-21) is administered at 10 mg/kg every 3 days for 4 weeks starting at EAE onset (score 1.0), THEN serum neurofilament light chain (NfL) concentrations will de | ≥35% reduction in serum NfL and ≥40% reduction in spinal cord MRI lesion volume | — no observation — | pending | 0.55 |
🔮 Falsifiable Predictions (2)
pendingconf 65%
IF CCR2+ monocytes are selectively depleted using CCR2-DTR bone marrow chimeric mice before EAE induction (via DT administration at 10 μg/g for 3 consecutive days), THEN clinical EAE scores will decrease by ≥40% and CNS infiltration of CD45+ immune cells will be reduced by ≥50% compared to control m
Predicted outcome: EAE clinical score reduction of ≥40% and CNS CD45+ cell count reduction of ≥50%
Falsification: No significant difference in EAE clinical scores or CNS immune cell infiltration between CCR2-depleted and control groups (p > 0.05 by Mann-Whitney U test)
pendingconf 55%
IF anti-CCR2 monoclonal antibody (clone MC-21) is administered at 10 mg/kg every 3 days for 4 weeks starting at EAE onset (score 1.0), THEN serum neurofilament light chain (NfL) concentrations will decrease by ≥35% and MRI-detected spinal cord lesion volume will be reduced by ≥40% compared to isotyp
Predicted outcome: ≥35% reduction in serum NfL and ≥40% reduction in spinal cord MRI lesion volume
Falsification: No significant reduction in serum NfL or MRI lesion volume between anti-CCR2 and isotype control groups (p > 0.05 by unpaired t-test); NfL increase of >20% would indicate treatment failure
▸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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