Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in podocytes | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 10 pathways; mostly protein handling | 0.90 |
Knock down and overexpress CTNND1 in microglia; measure proteasome activity and the load of ubiquitinated protein and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves proteasome activity by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of CTNND1 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CTNND1 in dopamine neurons, braak-0.45 (p 0.227) → -0.47 (p 0.197)receipt 16511
- CTNND1 in microglia, braak+0.26 (p 0.502) → +0.34 (p 0.374)receipt 16510
Swarm cases
receipt 16511: CTNND1 in dopamine neurons, braak
- power
- full sample -0.51 (p 0.031, n 18), 95% CI -0.79 to -0.06. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.56 (p 0.016, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.54 (p 0.021, n 18). not the mix.
- skeptic
- leave-one-out range -0.63 to -0.45, sign flips 0; without severely affected donors -0.51 (p 0.031, n 18). robust.
- cell type
- strongest in astrocytes: -0.61 (p 0.0075, n 18) vs -0.51 in dopamine neurons. proposing astrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CTNND1 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up CTNND1 · astrocytes · braak: substantia nigra, an independent cohort (already registered)
receipt 16510: CTNND1 in microglia, braak
- power
- full sample +0.26 (p 0.289, n 18), 95% CI -0.23 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.39 (p 0.109, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.37 (p 0.127, n 18). could be the mix.
- skeptic
- leave-one-out range +0.16 to +0.39, sign flips 0; without severely affected donors +0.26 (p 0.289, n 18). fragile.
- cell type
- strongest in astrocytes: -0.61 (p 0.0075, n 18) vs +0.26 in microglia. proposing astrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CTNND1 in microglia.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up CTNND1 · astrocytes · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.22 p 0.424 (needs p < 1.4e-4)
Receipts
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