Plasma fibrinogen leaks across the compromised BBB and undergoes coagulation cascade activation and cross-linking by factor XIII. Fibrin(ogen) deposition in the brain parenchyma triggers neuroinflammation via microglial CD18 integrin activation, while D-dimers (fibrin degradation products) enter systemic circulation. Elevated plasma D-dimer thus serves as a functional readout of BBB leakage with coagulation cascade activation—a vascular contribution biomarker distinct from purely neuronal markers like neurofilament light chain. D-dimer testing is widely standardized and clinically available, facilitating rapid validation.
Curated pathway from expert analysis
flowchart TD A["BBB Breakdown"] -->|"leakage"| B["Plasma fibrinogen leakage"] B -->|"cascade activation"| C["Coagulation cascade activation"] C -->|"cross-linking"| D["FXIII cross-linking"] D -->|"deposition"| E["Fibrin deposition in brain"] E -->|"integrin binding"| F["Microglial CD18 activation"] F -->|"pro-inflammatory"| G["Neuroinflammation"] G -->|"cytotoxic"| H["Neuronal loss and cognitive decline"] E -->|"degradation"| I["Fibrinolysis and D-dimer elevation"]
No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for FGA yet. Search RCSB →
Median TPM across 13 brain regions for FGA, FGB, FGG, D-dimer from GTEx v10.
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 FGA, FGB, FGG, D-dimer.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No resource usage or linked notebooks recorded for this hypothesis yet.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If plasma D-dimer elevation specifically reflects fibrinogen leakage through compromised BBB rather than systemic fibrinolysis, then D-dimer levels will correlate with BBB permeability markers (Qalb, | In paired plasma/CSF samples (n≥100) with postmortem tissue available, plasma D-dimer correlates with Qalb (r>0.5), sPDGFRβ (r>0.4), and brain parenchymal fibri | — no observation — | pending | 0.76 |