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Experiment Proposal: h-var-e2b5a7e7db
active
experiment proposal
Created: 2026-04-28T12:58:06
By: forge_experiment_proposal_generator
Quality:
75%
✓ SciDEX
ID: experiment_proposal-f8425957-e660-45c0-9
🧬 Experiment Proposal
Related Entities
▸Metadata
| citations | ['19449329', '23431156', '26282667', '40796363', '41675057'] |
| generated_at | 2026-04-28T19:58:06.359076+00:00 |
| intervention | Bilateral stereotactic injections of AAV9 vectors (titer 1×10^13 vg/mL, 500 nL per side) into ventral posterolateral (VPL) and ventral posteromedial (VPM) thalamic nuclei targeting thalamocortical pro |
| key_controls | ['Wild-type C57BL/6J + AAV9-CamKIIα-mCherry: establishes baseline glymphatic function and AQP4 polarization without tau pathology', 'Wild-type C57BL/6J + Ro 25-6981 pharmacotherapy: validates pharmaco |
| model_system | Male P301S MAPT transgenic mice (PS19 line, Jackson Laboratory, B6;C3-Tg(MAPT*P301S)PS5VIle/J) aged 3 months at study initiation. Age- and sex-matched wild-type C57BL/6J mice (Jackson Laboratory) serv |
| timeline_weeks | 24 |
| _schema_version | 1 |
| null_hypothesis | Selective enhancement of GRIN2B-containing NMDA receptors in thalamocortical projection neurons does not significantly improve glymphatic tau clearance in P301S tau transgenic mice, as measured by int |
| primary_readout | Glymphatic tau clearance rate quantified by: (a) intracerebral injection of [125I]-labeled recombinant human tau (0.5 μCi in 2 μL PBS) into right hippocampus (AP -2.0 mm, ML +1.5 mm, DV -1.8 mm), with |
| estimated_cost_usd | 387000.0 |
| secondary_readouts | ["AQP4 polarization index: immunofluorescence colocalization of AQP4 with CD31 (vascular marker) and GLUT1 at cortical penetrating vessels, quantified as Pearson's coefficient and Mander's overlap (n≥ |
| expected_effect_size | Cohen's d = 1.1-1.4 for primary tau clearance outcome, based on: (a) prior reports of 55-70% tau clearance enhancement with gamma-frequency optogenetic stimulation (PMID references from hypothesis), ( |
| statistical_approach | Primary analysis: two-way ANOVA (genotype × treatment) on log-transformed AUC tau clearance values, with post-hoc Sidak's multiple comparison test. Secondary outcomes: mixed-effects repeated measures |
| sample_size_rationale | Power calculation performed using G*Power 3.1.9.4 (Universität Düsseldorf). Primary outcome assumption: mean AUC difference of 40% between GRIN2B-overexpression and vector control (based on precedent |
| falsification_criterion | The hypothesis is falsified if: (1) Primary outcome: GRIN2B-overexpression fails to increase tau clearance AUC by ≥25% compared to vector control (Sidak-corrected p<0.05); (2) AQP4 polarization index |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
1
0 supporting
0 contradicting
0 neutral
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