Version history

{
  "description": "Why do entorhinal cortex layer II stellate neurons die first in AD? Their unique electrophysiological properties, grid cell function, and high metabolic demand may contribute, but the molecular basis of selective vulnerability is unknown.",
  "domain": "neurodegeneration",
  "status": "partially_addressed",
  "priority_score": 0.9,
  "importance_score": 0.9,
  "tractability_score": 0.75,
  "novelty_score": 0.7,
  "composite_score": 0.7002,
  "estimated_effort": "high",
  "source": "neurowiki",
  "evidence_summary": "{\"hypothesis_matches\": [{\"id\": \"h-var-3b982ec3d2\", \"title\": \"Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to block tau propagation and restore perforant-path gamma gating in Alzheimer's disease\", \"target_gene\": \"SST\", \"target_pathway\": \"Entorhinal cortex layer II SST interneuron-mediated perforant-path gamma gating and suppression of trans-synaptic tau propagation to hippocampus\", \"match_score\": 0.5, \"composite_score\": null, \"status\": \"proposed\"}, {\"id\": \"h-var-d98a992599\", \"title\": \"Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophagy flux and degrade intracellular tau before exosomal packaging in Alzheimer's disease\", \"target_gene\": \"SST\", \"target_pathway\": \"Entorhinal cortex layer II SST interneuron-driven GABAergic hyperpolarization activating AMPK-ULK1-beclin-1 autophagy flux to degrade tau oligomers before exosomal trans-synaptic propagation to hippocampus\", \"match_score\": 0.5, \"composite_score\": null, \"status\": \"proposed\"}, {\"id\": \"h-var-4eca108177\", \"title\": \"Closed-loop tACS targeting entorhinal cortex layer II parvalbumin interneurons to restore perisomatic gamma rhythmogenesis and block AnkyrinG-dependent tau-mediated axon initial segment disruption in Alzheimer's disease\", \"target_gene\": \"PVALB\", \"target_pathway\": \"Entorhinal cortex layer II\\u2013III PV interneuron perisomatic inhibition and AnkyrinG-dependent AIS integrity maintaining fast gamma rhythmogenesis and suppressing desynchronized tau-seeding burst activity in the perforant path\", \"match_score\": 0.5, \"composite_score\": null, \"status\": \"proposed\"}, {\"id\": \"h-var-14d7585dd1\", \"title\": \"Closed-loop tACS targeting entorhinal cortex layer II PV interneurons to suppress perisomatic burst firing and block tau propagation via the perforant path in Alzheimer's disease\", \"target_gene\": \"PVALB\", \"target_pathway\": \"Entorhinal cortex layer II PV interneuron-mediated perisomatic inhibition of stellate cells, suppression of high-frequency somatic bursting, and reduction of anterograde vesicular tau propagation via the perforant path\", \"match_score\": 0.5, \"composite_score\": null, \"status\": \"proposed\"}, {\"id\": \"h-var-55da4f915d\", \"title\": \"Closed-loop transcranial focused ultrasound targeting entorhinal cortex layer II SST interneurons to restore perforant-path gamma gating and block tau propagation in Alzheimer's disease\", \"target_gene\": \"SST\", \"target_pathway\": \"Entorhinal cortex layer II SST interneuron mechanosensitive activation via tFUS-driven PIEZO1/TREK-1 signaling, restoration of perforant-path gamma gating, and suppression of trans-synaptic tau propagation to hippocampus\", \"match_score\": 0.5, \"composite_score\": null, \"status\": \"proposed\"}, {\"id\": \"h-0f2b2111\", \"title\": \"Selective Neuronal Vulnerability Network Targeting\", \"target_gene\": \"Cell-type specific vulnerability markers\", \"target_pathway\": null, \"match_score\": 0.34, \"composite_score\": 0.4289470164217619, \"status\": \"proposed\"}, {\"id\": \"h_seaad_003\", \"title\": \"Layer V excitatory neurons show selectively enhanced vulnerability through dysregulated calcium signaling\", \"target_gene\": \"SLC17A7\", \"target_pathway\": null, \"match_score\": 0.2, \"composite_score\": 0.500720457565998, \"status\": \"proposed\"}], \"total_matching_hypotheses\": 7, \"gap_tokens_sample\": [\"AD\", \"II\", \"basis\", \"contribute\", \"cortex\", \"demand\", \"electrophysiological\", \"entorhinal\", \"first\", \"layer\", \"metabolic\", \"molecular\", \"neurons\", \"properties\", \"selective\"], \"updated_at\": \"2026-04-06T08:21:05.704160+00:00\"}",
  "resolution_criteria": "Resolved when: human, animal, or single-cell evidence identifies molecular features explaining selective vulnerability of entorhinal cortex layer II stellate neurons in AD, including electrophysiology/metabolic load, cell markers, and pathology timing. SciDEX must cite at least two studies or datasets, add KG edges for neuron subtype, region, molecular drivers, and AD pathology, and publish a scored mechanism hypothesis.",
  "market_price": 0.5
}