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Experiment Proposal: h-SDA-2026-04-26-gap-20260426-001521-01-plasma-nfl-elevation-secondary-to-bbb-associated-873d04c826
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experiment proposal
Created: 2026-04-28T12:59:47
By: forge_experiment_proposal_generator
Quality:
75%
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ID: experiment_proposal-afa14449-d6f1-4587-8
🧬 Experiment Proposal
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▸Metadata
| citations | ['38735950', '37875471', '33580742', '29377008', '30280653', '22048062'] |
| generated_at | 2026-04-28T19:59:47.148253+00:00 |
| intervention | Acute BBB modulation via intraperitoneal lipopolysaccharide (LPS, 1 mg/kg) or sterile saline (vehicle) at 3 timepoints: 24h, 72h, and 7 days post-injection. BBB integrity assessed via gadolinium-enhan |
| key_controls | ['Age-matched C57BL/6J WT mice treated with LPS (negative control for neurodegeneration-related NfL elevation)', 'Age-matched 5xFAD mice treated with sterile saline (vehicle control for LPS effects)', |
| model_system | C57BL/6J and 5xFAD transgenic mice (Alzheimer's disease model with amyloid pathology and progressive BBB dysfunction). Both sexes, 3 months and 9 months of age (pre-symptomatic and symptomatic stages) |
| timeline_weeks | 18 |
| _schema_version | 1 |
| null_hypothesis | Plasma NfL levels do not correlate with BBB permeability, and the plasma:CSF NfL ratio is not elevated in subjects with evidence of BBB disruption compared to those with intact BBB, indicating that pl |
| primary_readout | Plasma NfL concentration quantified by Simoa NF-Light Advantage assay (Quanterix) in pg/mL, measured in duplicate. Longitudinal plasma:CSF NfL ratio calculated at each timepoint. |
| estimated_cost_usd | 128500.0 |
| secondary_readouts | ['CSF NfL concentration by Simoa (parallel measurement to plasma)', 'BBB permeability markers: plasma soluble PDGFR-beta (sPDGFR-beta), CSF/serum albumin ratio, gadolinium enhancement volume on T1-wei |
| expected_effect_size | Cohen's d = 0.85 for plasma NfL elevation in 5xFAD vs. WT at 9 months (based on pilot data from PMID 38735950 indicating ~2.5-fold elevation). Power = 0.85 at alpha = 0.05 (two-tailed). For the primar |
| statistical_approach | Linear mixed-effects model with subject as random intercept for longitudinal plasma NfL and plasma:CSF ratio. Fixed effects: genotype (5xFAD vs. WT), time, treatment (LPS vs. saline), sex, and genotyp |
| sample_size_rationale | Power analysis (G*Power 3.1) based on two-way ANOVA for genotype×treatment interaction with effect size f = 0.40 (medium-large). With n=16 per group (accounting for 20% attrition from initial n=20), p |
| falsification_criterion | The hypothesis is falsified if: (1) plasma NfL levels do not differ significantly between 5xFAD and WT mice at 9 months (mixed-effects model p > 0.05), OR (2) the plasma:CSF NfL ratio is not elevated |
📊 Evidence Profile
Evidence Balance
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Certainty
0%
Debates
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Incoming
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Outgoing
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0 contradicting
0 neutral
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