Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.68 (overall 0.65) | 0.68 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 30 Parkinson's papers of 715 | 0.55 |
| pathways Reactome | 5 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress PSAP in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 PSAP in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.68; 2026-10-25 0.68; 2026-10-24 0.68; 2026-10-23 0.68.
Sealed predictions
- PSAP in dopamine neurons, braak-0.11 (p 0.778) → -0.01 (p 0.982)receipt 0529
- PSAP in dopamine neurons, resilience+0.31 (p 0.289) → -0.32 (p 0.240)receipt 0037
- PSAP in dopamine neurons, braak-0.16 (p 0.298) → +0.29 (p 0.058)receipt 0036
Swarm cases
receipt 0529: PSAP in dopamine neurons, braak
- power
- full sample +0.02 (p 0.928, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.949, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.09 (p 0.722, n 18). could be the mix.
- skeptic
- leave-one-out range -0.07 to +0.18, sign flips 7; without severely affected donors +0.02 (p 0.928, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PSAP in dopamine neurons.
case closed: nothing better to follow up.
receipt 0037: PSAP in dopamine neurons, resilience
- power
- full sample -0.02 (p 0.916, n 55), 95% CI -0.28 to +0.25. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.01 (p 0.966, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.00 (p 0.983, n 55). could be the mix.
- skeptic
- leave-one-out range -0.11 to +0.07, sign flips 6; without severely affected donors -0.08 (p 0.709, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for PSAP in dopamine neurons.
case closed: nothing better to follow up.
receipt 0036: PSAP in dopamine neurons, braak
- power
- full sample +0.05 (p 0.651, n 84), 95% CI -0.17 to +0.26. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.05 (p 0.681, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: +0.03 (p 0.776, n 84). could be the mix.
- skeptic
- leave-one-out range +0.03 to +0.08, sign flips 0; without severely affected donors +0.15 (p 0.186, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PSAP in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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