CSF soluble PDGFR-β shedding from pericytes as the earliest detectable molecular event in AD, preceding amyloid/tau pathology and exploitable as a 'zero-stage' biomarker via ADAM10/17-mediated ectodomain shedding. Biomarker utility is strong; therapeutic translation requires novel PDGFR-β agonism or ADAM10/17-selective CNS inhibition.
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.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF cognitively normal individuals aged 60-80 with elevated baseline CSF sPDGFR-β (top quartile) are stratified and followed longitudinally for 36 months, THEN they will demonstrate significantly faste | sPDGFR-β elevation precedes and predicts accelerated amyloid/tau pathology accumulation over 36 months, with effect size ≥15% difference in biomarker trajectori | — no observation — | pending | 0.65 |
| IF human brain pericytes in primary culture are treated with selective ADAM10 (Ro 28-1663) and ADAM17 (TMI-005) inhibitors either individually or in combination (25μM each, 48h), THEN combined ADAM10/ | sPDGFR-β shedding from pericytes requires coordinated ADAM10 and ADAM17 activity, with ≥60% reduction when both are inhibited simultaneously. | — no observation — | pending | 0.45 |