ID: hyp-sda-2026-04-01-gap-9137255b-2
Hypothesis
Membrane Lipid Composition-Dependent Specificity Switch Enabling Cross-Seeding Recognition
Specific lipid perturbations (bis(monoacylglycero)phosphate enrichment, cardiolipin externalization) create membrane microenvironments that expose distinct amyloid-competent conformers, allowing one misfolded protein to template another'.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 3 oppose
✓ All Quality Gates Passed
🧪 Overview
Specific lipid perturbations (bis(monoacylglycero)phosphate enrichment, cardiolipin externalization) create membrane microenvironments that expose distinct amyloid-competent conformers, allowing one misfolded protein to template another's beta-sheet formation with lipid-mediated specificity.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["Lysosomal Membrane Stress<br/>PLD3 Dysfunction or Mutation"]
B["BMP Bis-Monoacylglycerophosphate Enrichment<br/>Late Endosome Lipid Signature"]
C["Cardiolipin Externalization<br/>Mitochondrial Lipid Exposed"]
D["Membrane Microenvironment Switch<br/>Unique Lipid Topology Created"]
E["Amyloid-Competent Conformer Exposure<br/>Protein Misfolding Nucleation Sites"]
F["Cross-Seeding Recognition Events<br/>Specificity Switched by Lipid Context"]
G["Multi-Protein Aggregate Propagation<br/>Tau-SNCA-TDP43 Co-Seeding"]
A --> B
A --> C
B --> D
C --> D
D --> E
E --> F
F --> G
style D fill:#7b1fa2,stroke:#ce93d8,color:#ce93d8
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a⚖️ Evidence
⚖️ Evidence Matrix5 supports3 contradicts
Supports
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
Supports
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism.
Supports
PLD3 affects axonal spheroids and network defects in Alzheimer's disease.
Supports
PLD3 is a neuronal lysosomal phospholipase D associated with β-amyloid plaques and cognitive function in Alzheimer's disease.
Contradicts
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — PLD3
No curated PDB or AlphaFold mapping for PLD3 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 PLD3.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
No arena matches recorded yet. Browse Arenas →
📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0509
Events (7d)
0
Price History
▲5.2%💾 Resource Usage
LLM Tokens
10,754
$0.0444
Total Cost
$0.0444
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
Public annotations (0)Annotate on Hypothes.is →
No public annotations yet.