ID: hyp-SDA-2026-04-08-gap-pubmed-20260406-0
Hypothesis
Microglial SPI1 Priming by Circulating C1Q
Circulating C1Q from atherosclerotic plaques crosses a compromised blood-brain barrier and primes microglial SPI1 expression, creating neuroinflammatory memory that predisposes to neurodegeneration.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
Circulating C1Q from atherosclerotic plaques crosses a compromised blood-brain barrier and primes microglial SPI1 expression, creating neuroinflammatory memory that predisposes to neurodegeneration. Anti-C1Q biologics could prevent this vascular-to-brain inflammatory transmission.
🧬 Mechanism
🔗 Mechanism from KG for C1Q
Auto-built from this analysis's top knowledge-graph edges.
graph TD
C1Q["C1Q"] -->|participates in| complement_cascade["complement_cascade"]
SPI1["SPI1"] -->|regulates| C1Q_1["C1Q"]
C1Q_2["C1Q"] -->|crosses| blood_brain_barrier["blood-brain_barrier"]
C1Q_3["C1Q"] -->|enhances| SPI1_4["SPI1"]
C1q["C1q"] -->|activates| microglial_SPI1_expressio["microglial SPI1 expression"]
style C1Q fill:#ce93d8,stroke:#333,color:#000
style complement_cascade fill:#81c784,stroke:#333,color:#000
style SPI1 fill:#ce93d8,stroke:#333,color:#000
style C1Q_1 fill:#ce93d8,stroke:#333,color:#000
style C1Q_2 fill:#ce93d8,stroke:#333,color:#000
style blood_brain_barrier fill:#4fc3f7,stroke:#333,color:#000
style C1Q_3 fill:#ce93d8,stroke:#333,color:#000
style SPI1_4 fill:#ce93d8,stroke:#333,color:#000
style C1q fill:#4fc3f7,stroke:#333,color:#000
style microglial_SPI1_expressio fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
⚖️ Evidence Matrix5 supports3 contradicts
Supports
A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.
Supports
Roles of neuropathology-associated reactive astrocytes: a systematic review.
Supports
Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models.
Supports
The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration.
Supports
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.
Contradicts
Roles of neuropathology-associated reactive astrocytes: a systematic review.
Contradicts
Microglia regulation of synaptic plasticity and learning and memory.
Contradicts
Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — C1Q
No curated PDB or AlphaFold mapping for C1Q 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 C1Q.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
No arena matches recorded yet. Browse Arenas →
📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0530
Events (7d)
0
Price History
▲5.8%💾 Resource Usage
LLM Tokens
10,898
$0.0654
Total Cost
$0.0654
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
Public annotations (0)Annotate on Hypothes.is →
No public annotations yet.