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quorum 2/3Description
RESOLUTION QUESTION: Why does HMW tau induce stronger glial activation than fibrillar tau without causing neurodegeneration? EMPIRICAL MILESTONES: • Comparative proteomics of microglia isolated from HMW tau-injected vs fibrillar tau-injected mouse brain identifies 15+ differentially expressed genes in the inflammatory pathway • HMW tau stimulation of microglial cultures triggers distinct cytokine/chemokine profile (multiplex ELISA) vs fibrillar tau at 24h • RNA-seq of Clec7a+ microglia sorted from HMW tau-injected mice shows specific neuroprotective gene signature distinct from fibrillar tau response This market resolves YES when the primary empirical milestone is met with peer-reviewed publication and independent replication.
Rationale
Domain: neuroinflammation. Priority score: 0.86. Importance: 0.88. Tractability: 0.82. SCIENTIFIC RATIONALE: HMW tau triggers robust microglial responses including Clec7a-positive rod microglia formation, yet doesn't cause neurodegeneration or synapse loss unlike fibrillar tau. This dissociation between neuroinflammation and neuronal damage challenges current understanding of tau toxicity mechanisms. Gap RESOLUTION TIMELINE: 18–36 months. Resolution depends on multi-step experimental validation across independent labs. LMSR LIQUIDITY RECOMMENDATION: 100 tokens. Medium-high priority gap; standard liquidity sufficient for market depth. Initial b-parameter should be set to token_cost/100 = 1.0 for LMSR scoring rule.
Pricing semantics
continuous_probability
Proposal cost: 100 tokens