Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.72 (overall 0.68) | 0.72 |
| cell type Human Protein Atlas | group enriched in oligodendrocytes (379 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: zagotenemab, gosuranemab, bepranemab +3 | 0.81 |
| trials ClinicalTrials.gov | 20 Parkinson's trials, 0 stopped | 1.00 |
| literature PubMed | 682 Parkinson's papers of 2,812: well-trodden | 0.14 |
| pathways Reactome | 3 pathways; mostly other | 0.30 |
Knock down and overexpress MAPT in oligodendrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps; existing compounds already reach the inhibition arm.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 MAPT in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.63; 2026-10-25 0.63; 2026-10-24 0.63; 2026-10-23 0.63.
Sealed predictions
- MAPT in oligodendrocytes, braak-0.87 (p 0.002) → -0.09 (p 0.812)receipt 0525
- MAPT in dopamine neurons, braak-0.11 (p 0.773) → -0.25 (p 0.518)receipt 0526
- MAPT in oligodendrocytes, braak+0.07 (p 0.638) → +0.02 (p 0.902)receipt 0031
- MAPT in oligodendrocytes, resilience-0.16 (p 0.574) → -0.58 (p 0.033)receipt 0032
Swarm cases
receipt 0526: MAPT in dopamine neurons, braak
- power
- full sample -0.36 (p 0.148, n 18), 95% CI -0.71 to +0.13. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.32 (p 0.191, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.34 (p 0.173, n 18). could be the mix.
- skeptic
- leave-one-out range -0.48 to -0.28, sign flips 0; without severely affected donors -0.36 (p 0.148, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPT in dopamine neurons.
case closed: nothing better to follow up.
receipt 0525: MAPT in oligodendrocytes, braak
- power
- full sample -0.35 (p 0.153, n 18), 95% CI -0.70 to +0.14. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.31 (p 0.218, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.27 (p 0.273, n 18). could be the mix.
- skeptic
- leave-one-out range -0.56 to -0.30, sign flips 0; without severely affected donors -0.35 (p 0.153, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPT in oligodendrocytes.
case closed: nothing better to follow up.
receipt 0032: MAPT in oligodendrocytes, resilience
- power
- full sample -0.29 (p 0.135, n 55), 95% CI -0.52 to -0.03. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for age, sex and PMI: -0.26 (p 0.185, n 55). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis -0.52 (p 0.0075); controlling for it: -0.15 (p 0.449, n 55). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.22, sign flips 0; without severely affected donors -0.35 (p 0.087, n 46). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for MAPT in oligodendrocytes.
case closed: nothing better to follow up.
receipt 0031: MAPT in oligodendrocytes, braak
- power
- full sample +0.05 (p 0.635, n 84), 95% CI -0.16 to +0.26. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.02 (p 0.839, n 84). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.09 (p 0.422); controlling for it: +0.00 (p 0.988, n 84). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.08, sign flips 0; without severely affected donors +0.12 (p 0.314, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for MAPT in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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