Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.32 (overall 0.20) | 0.32 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in choroid plexus epithelial cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| 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 | in no curated pathway | 0.00 |
Knock down and overexpress LDLRAD4 in microglia; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 LDLRAD4 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- LDLRAD4 in microglia, braak+0.00 (p 1.000) → -0.32 (p 0.407)receipt 2045
- LDLRAD4 in dopamine neurons, braak-0.27 (p 0.474) → -0.27 (p 0.476)receipt 2046
Swarm cases
receipt 2046: LDLRAD4 in dopamine neurons, braak
- power
- full sample -0.34 (p 0.173, n 18), 95% CI -0.69 to +0.16. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.32 (p 0.194, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.26 (p 0.298, n 18). could be the mix.
- skeptic
- leave-one-out range -0.45 to -0.24, sign flips 0; without severely affected donors -0.34 (p 0.173, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LDLRAD4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2045: LDLRAD4 in microglia, braak
- power
- full sample -0.18 (p 0.471, n 18), 95% CI -0.60 to +0.31. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.12 (p 0.627, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.10 (p 0.702, n 18). could be the mix.
- skeptic
- leave-one-out range -0.33 to -0.06, sign flips 0; without severely affected donors -0.18 (p 0.471, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LDLRAD4 in microglia.
case closed: nothing better to follow up.
Receipts
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