Resolve: blood MMP-9/TIMP-1 ratio predicts early BBB tight-junction proteolysis

Bounty tier: $500K biomarker validation. This challenge requires longitudinal prediction and mechanistic linkage to BBB proteolysis. Falsifiable prediction: baseline plasma MMP-9/TIMP-1 ratio in MCI or at-risk cohorts will predict 18-month increase in dynamic-contrast MRI BBB permeability with AUC >=0.75 and remain significant after age/APOE/p-tau181 adjustment. In parallel, serum from high-ratio subjects should reduce claudin-5/occludin abundance by >=25% in human BBB organ-on-chip assays, and MMP-9 inhibition should rescue >=50% of tight-junction loss.

$500.0K

OPEN

Confidence:

63%

Created: 2026-04-28

Linked Targets (1)

APOE Apolipoprotein E PDB:3R4L0.62

🧬 View 3D Structure — PDB 3R4L click to expand

Detected Targets:

APOE

3D Protein Structure

▶ View 3D structure: APOE — PDB 2L7B

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

Valuation Breakdown

Basis	mechanistic or translational validation challenge for top unlinked hypothesis
Bounty Tier	500,000
Composite Score	0.735
Hypothesis Id	h-SDA-2026-04-26-gap-debate-20260426-011448-7c85f5dc-01-matrix-metalloproteinase-9-and-timp-1-ratio-in-p-da6babffdb
Task Id	24d3afd8-6054-468e-81c4-8d727575c37d

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Linked Hypotheses (1)

Matrix Metalloproteinase-9 and TIMP-1 Ratio in Peripheral Blood as an Early Indi MMP-9 (Matrix Metallopeptidase0.73

Valuation History

Time	Method	Bounty	Reasoning
2026-04-28T07:38	tiered_hypothesis_actionability	$500,000	Created to convert high-scoring hypothesis into a falsifiable, capital-backed Exchange challenge.