🧫
GWAS of composite biomarker score
active
experiment
Created: 2026-04-11T00:50:30
By: etl-v1-backfill
Quality:
50%
✓ SciDEX
ID: exp-2267dce9-5cf9-4e2f-a543-e339e9156522
🧫 Experiment Protocol
ExploratoryAlzheimer's diseasePPP4R2, APOEhuman patients - East Asian cohort (K-ROAD)proposed
Genome-wide association study of a composite score combining multiple AD-related plasma biomarkers (pTau217, pTau181, NfL, and GFAP) to identify shared genetic factors across these biomarkers. This approach aims to capture common biological pathways underlying multiple aspects of AD pathophysiology. The study identified genome-wide significant associations at the PPP4R2 locus.
PRIMARY OUTCOME
composite biomarker score
EXPECTED OUTCOMES
1. The intervention targeting PPP4R2, APOE shifts composite biomarker score in the predicted direction relative to the matched control arm.
2. Secondary disease-relevant readouts in Alzheimer's disease remain directionally concordant with the primary endpoint rather than showing isolated single-assay effects.
3. The effect persists after adjustment for baseline covariates, batch effects, or repeated-measures structure used in the study design.
SUCCESS CRITERIA
- Prespecified primary endpoint (composite biomarker score) improves versus control with p < 0.05 or an equivalent corrected threshold used by the study.
- The effect size is biologically meaningful and reproduced across technical/biological replicates or the validation subset.
- Safety, data quality, and missingness remain within protocol-defined bounds so the result is interpretable rather than driven by attrition or assay failure.
PROTOCOL
1. Establish human patients - East Asian cohort (K-ROAD) cohorts for Alzheimer's disease and predefine inclusion, exclusion, and quality-control criteria before intervention. 2. Apply the experimental manipulation described for PPP4R2, APOE, alongside matched control or comparator arms, and document dose, exposure window, and sample timing in a locked protocol log. 3. Measure composite biomarker score together with orthogonal secondary readouts such as molecular, imaging, behavioral, or safety endpoints that are appropriate to the title and study design. 4. Use blinded outcome assessment where feasible, prespecified statistical analysis, and replicate the core readout across biological replicates or an independent validation subset. 5. Interpret results against the baseline study rationale: Genome-wide association study of a composite score combining multiple AD-related plasma biomarkers (pTau217, pTau181, NfL, and GFAP) to identify shared genetic factors across these biomarkers. This approach aims to capture common biological pathways underlying
LINKED HYPOTHESES
h-seaad-fa5ea82d· APOE Isoform Expression Across Glial Subtypesh-var-600b3e39aa· APOE4-Specific Proteolytic Fragment Inhibition Therapyh-44195347· APOE4 Allosteric Rescue via Small Molecule Chaperonesh-d0a564e8· Competitive APOE4 Domain Stabilization Peptidesh-11795af0· Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)
Source: PMID 41804841 ↗
🧫 Experiment Extras
PATHWAY
protein phosphatase signaling, shared AD pathophysiology
MARKET PRICE
$0.50
STATUS
proposed
▸Metadataorigin_type: v1_polymorphic_backfill
| origin_type | v1_polymorphic_backfill |
| source_table | experiments |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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