{"artifact":{"id":"experiment-exp-debate-385d65cb42cb","artifact_type":"experiment","entity_ids":null,"title":"Proposed experiment from debate on Synaptic pruning by microglia in early AD","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"debate_extraction","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.910736Z"},"summary":"# Proposed experiment from debate on Synaptic pruning by microglia in early AD\n## Background and Rationale\n# Expanded Experimental Description: CX3CR1-Targeted Positive Allosteric Modulators in Alzheimer's Disease Neuroinflammation\n\nThe proposed investigation addresses a critical gap in understanding the role of microglial CX3CR1 signaling in synaptic preservation during early Alzheimer's disease pathogenesis. 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Administration (Weeks 3-14)**\n• Prepare CX3CR1 PAMs: selective compound JMS-17-2 (microglia-specific) and broad-spectrum compound AZD8797\n• Administer treatments via osmotic minipumps: vehicle control, low dose (1 mg/kg/day), medium dose (5 mg/kg/day), high dose (15 mg/kg/day)\n• Monitor body weight, motor function, and general health weekly\n• Collect blood samples at weeks 6, 9, and 12 for peripheral inflammatory markers\n\n**Phase 3: Neuroinflammatory Assessment (Weeks 12-14)**\n• Harvest brain tissue from n=8 mice per group ","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.910742","needs_review":true,"extraction_notes":"Backfilled from debate_extraction source (no PMID 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APP"},{"target_artifact_id":"wiki-mechanisms-tgf-beta-signaling-cbs-psp","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: TGF"},{"target_artifact_id":"wiki-therapeutics-aav-vectors-neurodegenerative-gene-therapy","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: AAV"},{"target_artifact_id":"wiki-mechanisms-tgf-beta-parkinsons","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: TGF"},{"target_artifact_id":"wiki-genes-ccr1","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: CCR1"},{"target_artifact_id":"wiki-diseases-cns-vasculitis","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: CNS"},{"target_artifact_id":"wiki-genes-synaptophysin","link_type":"related","strength":0.54,"evidence":"Reverse: Title match: synaptophysin"},{"target_artifact_id":"wiki-therapeutics-csf1r-modulation-therapy","link_type":"related","strength":0.63,"evidence":"Reverse: Gene mention: 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wiki/cell-types-enteric-glia"},{"source_artifact_id":"wiki-mechanisms-anti-amyloid-therapeutics","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/mechanisms-anti-amyloid-therapeutics"},{"source_artifact_id":"wiki-technologies-rna-editing-therapeutics","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/technologies-rna-editing-therapeutics"},{"source_artifact_id":"wiki-technologies-digital-therapeutics","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/technologies-digital-therapeutics"},{"source_artifact_id":"wiki-biomarkers-progranulin","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 4x in wiki/biomarkers-progranulin"},{"source_artifact_id":"wiki-companies-ad-rna-therapeutics","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/companies-ad-rna-therapeutics"},{"source_artifact_id":"wiki-organizations-denali-therapeutics","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/organizations-denali-therapeutics"},{"source_artifact_id":"wiki-diseases-lewy-body-dementia","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 3x in wiki/diseases-lewy-body-dementia"},{"source_artifact_id":"wiki-cell-types-spinal-cord-microglia-chronic-pain","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: CX3CR1 mentioned 2x in wiki/cell-types-spinal-cord-microglia-chronic-pain"},{"source_artifact_id":"wiki-cx3cr1","link_type":"mentions","strength":0.7,"evidence":"Experiment targets CX3CR1"},{"source_artifact_id":"wiki-cell-types-microglia","link_type":"mentions","strength":0.4,"evidence":"Related to disease: Neuroinflammation"},{"source_artifact_id":"wiki-entities-microglia","link_type":"mentions","strength":0.4,"evidence":"Related to disease: Neuroinflammation"},{"source_artifact_id":"wiki-neuroinflammation","link_type":"mentions","strength":0.4,"evidence":"Related to disease: Neuroinflammation"},{"source_artifact_id":"wiki-microglia","link_type":"mentions","strength":0.4,"evidence":"Related to disease: Neuroinflammation"},{"source_artifact_id":"wiki-mechanisms-neuroinflammation","link_type":"mentions","strength":0.4,"evidence":"Related to disease: Neuroinflammation"},{"source_artifact_id":"wiki-genes-cx3cr1","link_type":"mentions","strength":0.7,"evidence":"Experiment targets CX3CR1"},{"source_artifact_id":"wiki-proteins-cx3cr1-protein","link_type":"mentions","strength":0.8,"evidence":"Gene target: CX3CR1"},{"source_artifact_id":"wiki-investment-aav-gene-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-mechanisms-bbb-transport-mechanisms","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BBB"},{"source_artifact_id":"wiki-mechanisms-app-ps1-double-transgenic-mouse","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-entities-tnf","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-proteins-csf1r","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-mechanisms","link_type":"mentions","strength":0.6,"evidence":"Title match: Mechanisms"},{"source_artifact_id":"wiki-entities-app","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-genes-tnfa","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-diseases-app-mutations-in-ad","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-investment-tgf-beta-signaling-therapeutics-investment-analysis","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-proteins-tgf-beta1-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-ideas-csf1r-microglia-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-genes-snap25","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNAP25"},{"source_artifact_id":"wiki-cell-types-central-nervous-system-border-immune-cells","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CNS"},{"source_artifact_id":"wiki-cell-types-cx3cr1-neurons","link_type":"mentions","strength":0.8,"evidence":"Gene target: CX3CR1"},{"source_artifact_id":"wiki-cell-types-blood-brain-barrier","link_type":"mentions","strength":0.6,"evidence":"Title match: Blood-Brain Barrier"},{"source_artifact_id":"wiki-diseases-alzheimers-disease","link_type":"mentions","strength":0.6,"evidence":"Title match: Alzheimer's 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synaptophysin"},{"source_artifact_id":"wiki-therapeutics-csf1r-modulation-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-genes-csf1r","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-genes-tnf","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-ideas-payload-app-dosage-reduction-ds-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-genes-app","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-cell-types-dendritic-spine-neurons","link_type":"mentions","strength":0.6,"evidence":"Title match: Dendritic Spines"},{"source_artifact_id":"wiki-proteins-snap-25","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNAP25"},{"source_artifact_id":"wiki-therapeutics-cx3cr1-modulation-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CX3CR1"},{"source_artifact_id":"wiki-mechanisms-tgf-beta-hs3st2-tau-axis","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-mechanisms-cns-drug-delivery-methods","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CNS"},{"source_artifact_id":"wiki-ideas-payload-aav-capsid-engineering-cns-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-experiments-aav-lrrk2-ind-enabling-studies","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-mechanisms-aav-gene-therapy-vectors-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-proteins-app","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-mechanisms-app-amyloid-beta-plaque-ad-causal-chain","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-ideas-payload-cx3cr1-modulation-therapy","link_type":"mentions","strength":0.8,"evidence":"Gene target: CX3CR1"},{"source_artifact_id":"wiki-models-app-ps1-dual-transgenic-model","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-ideas-cns-nlrp3-inflammasome-inhibitor","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CNS"},{"source_artifact_id":"wiki-experiments-lrrk2-aav-ind-enabling-study","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-mechanisms-blood-brain-barrier","link_type":"mentions","strength":0.6,"evidence":"Title match: Blood-Brain Barrier"},{"source_artifact_id":"wiki-proteins-psd93-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PSD"},{"source_artifact_id":"wiki-mechanisms-cx3cr1-pet-imaging-microglia","link_type":"mentions","strength":0.8,"evidence":"Gene target: CX3CR1"},{"source_artifact_id":"wiki-therapeutics-bbb-penetrant-antibodies","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BBB"},{"source_artifact_id":"wiki-ideas-csf1r-modulation-microglia-reset","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-mechanisms-cns-lymphatic-meningeal-immunity-4r-tauopathies","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CNS"},{"source_artifact_id":"wiki-proteins-tgfbr1-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-cell-types-csf1r-inhibited-microglia","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-cell-types-app-overexpressing-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-mechanisms-tau-pathology","link_type":"mentions","strength":0.6,"evidence":"Title match: Tau Pathology"},{"source_artifact_id":"wiki-proteins-tnf-alpha-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-proteins-snap25","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNAP25"},{"source_artifact_id":"wiki-ideas-payload-aav-rna-targeting-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-therapeutics-csf1r-inhibitors-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CSF1R"},{"source_artifact_id":"wiki-mechanisms-tnf-signaling-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-genes-tmem119","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TMEM119"},{"source_artifact_id":"wiki-ideas-bbb-transcytosis-shuttle-protac-delivery","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BBB"},{"source_artifact_id":"wiki-mechanisms-app-bace1-fe65-complex","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-proteins-psd-95-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PSD"},{"source_artifact_id":"wiki-proteins-tnf-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TNF"},{"source_artifact_id":"wiki-experiments-aaav-serotype-lrrk2-gene-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-genes-ccr5","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CCR5"},{"source_artifact_id":"wiki-therapeutics-aav-gene-therapy-neurodevelopmental-epilepsy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-ideas-payload-tgf-beta-activator-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-ideas-bbb-transcytosis-protac","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BBB"},{"source_artifact_id":"wiki-ideas-payload-aav-serotype-cns-delivery-optimization-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-entities-psd-95","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PSD"},{"source_artifact_id":"wiki-mechanisms-app-processing","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-proteins-tgfrb1-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-proteins-ccr5","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CCR5"},{"source_artifact_id":"wiki-therapeutics-aav-gene-therapy-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-models-aav-lrrk2-gene-delivery-model","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-mechanisms-tgf-beta-signaling-pathway","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-proteins-cx3cl1-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CX3CL1"},{"source_artifact_id":"wiki-proteins-ccr5-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CCR5"},{"source_artifact_id":"wiki-mechanisms-tgf-beta-bmp-signaling-pathway","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-mechanisms-tgf-beta-signaling-neurodegeneration","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-diseases-app-swedish-mutation","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-experiments-aav-serotype-lrrk2-knockdown","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-therapeutics-aav-cns-gene-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-therapeutics-tgf-beta-modulation-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-diseases-app-flemish-mutation","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-proteins-tgfrb2-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-proteins-tgfb1-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-genes-cx3cl1","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CX3CL1"},{"source_artifact_id":"wiki-technologies-aav-vectors","link_type":"mentions","strength":0.7,"evidence":"Gene mention: AAV"},{"source_artifact_id":"wiki-genes-p2ry12","link_type":"mentions","strength":0.7,"evidence":"Gene mention: P2RY12"},{"source_artifact_id":"wiki-therapeutics-tgfb-signaling-therapeutics","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-proteins-tmem119-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TMEM119"},{"source_artifact_id":"wiki-mechanisms-alzheimers-pathogenesis","link_type":"mentions","strength":0.6,"evidence":"Title match: Alzheimer's Disease Pathogenesis"},{"source_artifact_id":"wiki-proteins-psd95-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PSD"},{"source_artifact_id":"wiki-cell-types-ccr5-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CCR5"},{"source_artifact_id":"wiki-ideas-payload-tgf-beta-modulation-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: TGF"},{"source_artifact_id":"wiki-mechanisms-fear-conditioning","link_type":"mentions","strength":0.6,"evidence":"Title match: Fear Conditioning"},{"source_artifact_id":"wiki-mechanisms-app-amyloid-pathway-alzheimers","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-cell-types-dendritic-spines","link_type":"mentions","strength":0.6,"evidence":"Title match: Dendritic Spines"},{"source_artifact_id":"wiki-diseases-app-arctic-mutation","link_type":"mentions","strength":0.7,"evidence":"Gene mention: APP"},{"source_artifact_id":"wiki-diseases-neurodegeneration","link_type":"mentions","strength":0.6,"evidence":"Title match: 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experiment"},{"source_artifact_id":"wiki-proteins-synaptophysin-protein","link_type":"mentions","strength":0.6,"evidence":"Wiki page 'Synaptophysin Protein' mentions entity found in experiment"},{"source_artifact_id":"hypothesis-h-782b40b1","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-debate-385d65cb42cb"},{"source_artifact_id":"hypothesis-h-5daecb6e","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-debate-385d65cb42cb"},{"source_artifact_id":"hypothesis-h-f99ce4ca","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-debate-385d65cb42cb"},{"source_artifact_id":"hypothesis-h-0758b337","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-debate-385d65cb42cb"},{"source_artifact_id":"wiki-therapeutics-section-147-neuroimmune-glial-crosstalk-cbs-psp","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 4x in wiki/therapeutics-section-147-neuroimmune-glial-crosstalk-cbs-psp"},{"source_artifact_id":"wiki-therapeutics-microglia-modulation-therapy-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 4x in wiki/therapeutics-microglia-modulation-therapy-neurodegeneration"},{"source_artifact_id":"wiki-therapeutics-neuroinflammation-modulation-therapies","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 4x in wiki/therapeutics-neuroinflammation-modulation-therapies"},{"source_artifact_id":"wiki-therapeutics-chemokine-receptor-modulation-parkinsons","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 32x in wiki/therapeutics-chemokine-receptor-modulation-parkinsons"},{"source_artifact_id":"wiki-therapeutics-microglial-modulation-therapy","link_type":"mentions","strength":0.5,"evidence":"Content: CX3CR1 mentioned 5x in 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