Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.94 (overall 0.87) | 0.94 |
| cell type Human Protein Atlas | cell type enhanced, including other brain neurons; strongest in retinal ganglion cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | 1 Parkinson's trial, 0 stopped | 1.00 |
| literature PubMed | 336 Parkinson's papers of 433 | 0.23 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress ATP13A2 in dopamine neurons; measure a transcriptome-wide state shift (bulk RNA-seq) and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.
- Cell type
- dopamine neurons
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
- 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 ATP13A2 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.65; 2026-10-25 0.61; 2026-10-24 0.65; 2026-10-23 0.61.
Sealed predictions
- ATP13A2 in dopamine neurons, braak-0.34 (p 0.028) → -0.44 (p 0.004)held
- ATP13A2 in dopamine neurons, braak+0.49 (p 0.186) → -0.23 (p 0.549)receipt 0508
- ATP13A2 in dopamine neurons, resilience+0.23 (p 0.364) → -0.29 (p 0.374)receipt 0005
In the sealed studies
- The lysosomal axis in dopamine neurons: did not hold
Swarm cases
receipt 0508: ATP13A2 in dopamine neurons, braak
- power
- full sample +0.07 (p 0.794, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.06 (p 0.827, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.11 (p 0.671, n 18). could be the mix.
- skeptic
- leave-one-out range -0.04 to +0.20, sign flips 4; without severely affected donors +0.07 (p 0.794, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ATP13A2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0005: ATP13A2 in dopamine neurons, resilience
- power
- full sample +0.07 (p 0.736, n 55), 95% CI -0.20 to +0.33. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: +0.15 (p 0.449, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: +0.02 (p 0.933, n 55). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.14, sign flips 1; without severely affected donors +0.04 (p 0.847, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- braak beats resilience for ATP13A2 in dopamine neurons: -0.40 (p 1.8e-4, n 84). proposing braak.
case closed: every proposal failed a challenge.
Receipts
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