The "Trans-Cellular Prion-Like Propagation of Transcriptional Memory" Model
🧪 Overview
Rather than treating cell-type specific expression patterns as static features, I propose that SEA-AD involves a propagating wave of epigenetic "conditioning" wherein neurons that encounter tau or amyloid oligomers undergo reversible chromatin remodeling (through BRG1/BAF complex and polycomb repression shifts), establishing a temporary but communicable transcriptional state that can be transferred to naive neighboring cells via extracellular vesicles (EVs) carrying modified histone reader proteins and non-coding RNAs. This would mean that apparent cell-type specificity reflects not intrinsic cellular identity, but rather spatial-temporal "infection" of transcriptional state. Microglia, which efficiently internalize pathological EVs, would become secondary propagators—not primary drivers—of neuroinflammatory gene expression. Testable predictions: (1) EVs from tau-exposed neurons (in vitro or
🧬 Mechanism
Auto-built from this analysis's top knowledge-graph edges.
graph TD
SLC17A7["SLC17A7"] -->|associated with| Alzheimer_s_Disease["Alzheimer's Disease"]
C1QA["C1QA"] -->|associated with| Alzheimer_s_Disease_1["Alzheimer's Disease"]
SLC17A7_2["SLC17A7"] -->|associated with| alzheimer_s_disease["alzheimer_s_disease"]
debate_seaad_20260402["debate-seaad-20260402"] -->|causal extracted| processed["processed"]
style SLC17A7 fill:#ce93d8,stroke:#333,color:#000
style Alzheimer_s_Disease fill:#ef5350,stroke:#333,color:#000
style C1QA fill:#ce93d8,stroke:#333,color:#000
style Alzheimer_s_Disease_1 fill:#ef5350,stroke:#333,color:#000
style SLC17A7_2 fill:#ce93d8,stroke:#333,color:#000
style alzheimer_s_disease fill:#ef5350,stroke:#333,color:#000
style debate_seaad_20260402 fill:#4fc3f7,stroke:#333,color:#000
style processed fill:#4fc3f7,stroke:#333,color:#000⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — SEA
No curated PDB or AlphaFold mapping for SEA yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for SEA.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_round_mining
| source | v1_phase_c_backfill |
| origin_type | debate_round_mining |
| _schema_version | 1 |