Therapeutic benefit from pericyte-directed senescence interventions depends on stage. If BBB leak and dysfunction occur while PDGFRB+ pericytes are still present but senescent-like, intervention may be disease-modifying; once dropout dominates, senolysis may be ineffective or harmful. This is best treated as a trial-enrichment and therapeutic-window hypothesis rather than a primary biology claim.
Curated pathway from expert analysis
flowchart TD
A["PDGFRB Activation<br/>PDGF-BB Ligand Binding"]
B["Pericyte Recruitment<br/>Blood-Brain Barrier Maintenance"]
C["PDGFRB Signaling<br/>PI3K/AKT and MAPK Pathways"]
D["Pericyte Coverage<br/>Capillary Integrity"]
E["BBB Integrity Loss<br/>Pericyte Dropout in AD"]
F["Neurovascular Coupling<br/>Functional Hyperemia Impaired"]
G["Amyloid Deposition<br/>Cerebral Amyloid Angiopathy"]
H["Hypoperfusion<br/>Chronic Ischemia"]
I["Cognitive Decline<br/>Vascular contributions to dementia"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> H
E --> G
G --> H
H --> I
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style I fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for PDGFRB yet. Search RCSB →
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 PDGFRB, CDKN2A, CDKN1A, BCL2, BCL2L1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF APPSWE/PSEN1*E9 or P301S transgenic mice receive pericyte-directed senomorphic therapy targeting PDGFRB-BCL2L1 signaling (e.g., BCL-XL sparing senomorphic or PDGFRB agonist that normalizes BCL2L1 e | Early senomorphic treatment preserves pericyte coverage at ≥70%, prevents BBB leakage increase to ≤20% above baseline, and maintains spatial memory performance | — no observation — | pending | 0.55 |
| IF patients with early-stage Alzheimer's disease (CDR 0.5-1.0) stratified by cerebrospinal fluid or PET evidence of PDGFRB+ pericyte senescence (elevated p16INK4a/CDKN2A co-localized with PDGFRB) rece | CSF/plasma fibrinogen ratio reduced ≥30% and hippocampal atrophy limited to ≤2% in early senescent-but-retained pericyte subgroup receiving senolytic, with no s | — no observation — | pending | 0.45 |