Neurogranulin Predicts p-tau217 Reliability by Identifying Patients with Intact Neuronal Reserve
🧪 Overview
Neurogranulin (Ng) is a postsynaptic protein correlating with cognitive reserve. Low Ng indicates depleted neuronal capacity to produce p-tau217, making CSF p-tau217 unreliable. Patients with preserved Ng levels show faithful p-tau217 response to amyloid modulation. This hypothesis addresses a potentially critical prerequisite for valid p-tau217 endpoints but remains the lowest-confidence proposal requiring prospective validation.
🧬 Mechanism
Curated pathway from expert analysis
graph TD
A["Neurogranulin NRGN expression level"] --> B["Intact neuronal reserve capacity index"]
B --> C["Favorable amyloid modulation response profile"]
C --> D["Reliable CSF p-tau217 as Alzheimer's progression marker"]
D --> E["Accurate patient stratification for anti-amyloid therapy"]⚖️ Evidence
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — NRGN
No curated PDB or AlphaFold mapping for NRGN yet. Search RCSB →
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for NRGN from GTEx v10.
💉 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 NRGN.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
📊 Market Indicators
💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF we compare longitudinal CSF p-tau217 measurements (baseline, 6 months, 12 months) in amyloid-positive patients with low CSF Ng (below 25th percentile) versus preserved CSF Ng (above 75th percentile | Preserved Ng group ICC: 0.89 (95% CI: 0.82-0.94); Low Ng group ICC: 0.52 (95% CI: 0.38-0.67); CV in low Ng group >20% vs <8% in preserved Ng group | — no observation — | pending | 0.18 |
| IF we stratify amyloid-positive early Alzheimer's disease patients by baseline CSF neurogranulin (Ng) levels into high (upper tertile) and low (lower tertile) groups AND administer an amyloid-targetin | High Ng group: mean CSF p-tau217 reduction of 45% (95% CI: 38-52%); Low Ng group: mean CSF p-tau217 reduction of 12% (95% CI: 5-19%); between-group difference p | — no observation — | pending | 0.15 |
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |