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Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial

PARTIALLY ADDRESSED

Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial dysregulation (0.56), GFAP reactive astrocytosis (0.536). Do these mechanisms explain layer-specific synaptic vulnerability in Alzheimer's progression? [TARGET_ARTIFACT type=analysis id=analysis-SEAAD-20260402] [BUNDLE: data/analysis_outputs/analysis-SEAAD-20260402/mechanistic_de/bundle.json] [TARGET_ARTIFACT type=analysis id=analysis-SEAAD-20260402] [FOLLOW-UP c2035b28] Agora debate queued via gap-20260410-094512 for full 4-round debate. Original debate quality was 0.65 (3 rounds only, missing Skeptic and Expert). Bundle from computational_biologist agent.

Priority: 0.90 Domain: neurodegeneration Hypotheses: 0
📊 Landscape Analysis

Landscape Summary: Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial is a 0.9 priority gap in neurodegeneration. It has 0 linked hypotheses with average composite score 0.000. Status: partially_addressed.

Key Unanswered Questions

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

Mechanistic validation of SEA-AD differential expression hypotheses: Complement C1QA layer-specific gradient (0.646), TREM2 DAM upregulation (0.576), VGLUT1 excitatory neuron loss (0.567), APOE4 glial — INVOKE-2 (completed)

📈 Living Dashboards
0
Hypotheses
0.000
Top Score
0.000
Avg Score
2
Debates
0.65
Avg Quality
60%
Resolution
0
Mechanistic Families
Gap Resolution Progress60%

Hypothesis Score Distribution

🏆 Competing Hypotheses (Ranked by Score)

No hypotheses linked to this gap yet.

🌊 Knowledge Graph Connections

activates (24)

ASTROCYTES→ComplementCYTOKINES→ComplementCOMPLEMENT→ComplementTREM2→ALZHEIMER'S DISEASEALZHEIMER'S DISEASE→Complement
▸ Show 19 more

associated with (4)

MICROGLIA→TREM2TREM2→ALZHEIMERTREM2→ALZHEIMERSAPOE4→Aging

data in (3)

ad_genetic_risk_loci:TREM2→TREM2TREM2→benchmark_ot_ad_answer_key:TREM2benchmark_ot_ad_answer_key:TREM2→TREM2

disrupts (1)

APOE4→intracellular lipid homeostasis

encodes (1)

APOE4→APOE4

expressed in (2)

TREM2→MICROGLIAAPOE4→Alzheimer

inhibits (2)

COMPLEMENT→ComplementTREM2→Inflammation

predicts (1)

APOE4→cognitive decline

regulates (3)

Inflammation→ComplementTREM2→MICROGLIAAls→Complement

relates to (4)

h-immunity-c3bc272f→TREM2h-immunity-c64967ab→APOE4h-immunity-c3bc272f→C1QAh-immunity-c64967ab→TREM2

therapeutic target (5)

CANCER→ComplementTREM2→InflammationTREM2→NeuroinflammationAls→ComplementCancer→Complement
🕑 Activity Feed
✏ update on knowledge_gap by max_outlook1 2026-04-28T01:37
✏ update on knowledge_gap by None 2026-04-25T22:15
🎭 Mechanistic validation of SEA-AD differential expression hyp q=0.66 2026-04-21T08:19
🎭 Mechanistic validation of SEA-AD differential expression hyp q=0.64 2026-04-21T08:10
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