Resolve: Microglial TREM2-Complement Axis Modulation

Falsifiable prediction from high-scoring hypothesis (score=0.726, gene=TREM2 and C3). Hypothesis: Can selective modulation of the TREM2-C3 axis (TREM2 agonism + C3 inhibition) simultaneously restore microglial phagocytosis and block complement-mediated synaptic pruning in AD? Success criteria: 1. TREM2 agonist (AL002c) + C3 inhibitor (avacopan) co-treatment increases amyloid-beta uptake by >50% vs single agent. 2. C3a generation (ELISA) is reduced by >60% in activated microglia co-treated vs TREM2 agonist alone. 3. Synaptic marker (PSD95) intensity is preserved (>85% vs sham) in 5xFAD mice co-treated vs >40% loss in vehicle. 4. Cognitive function (Morris water maze) improves by >25% in co-treatment group vs single-agent controls.

$500
OPEN
Confidence:
50%
Created: 2026-04-28

Linked Targets (2)

C3 Complement C3 PDB:2A730.67
🧬 View 3D Structure — PDB 2A73 click to expand

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TREM2 Triggering receptor expressed on myeloid cells 2 PDB:5UD70.63
🧬 View 3D Structure — PDB 5UD7 click to expand

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Detected Targets:
TREM2

3D Protein Structure

View 3D structure: TREM2 — PDB 6YXY

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

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Linked Hypotheses (1)

Microglial TREM2-Complement Axis Modulation TREM2 and C30.73