Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

GNAI1

G protein subunit alpha i1

translation score 0.61, read 2026-10-24; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.02 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced in oligodendrocytes (506 nCPM)1.00
chemistry
Open Targets		a small-molecule pocket0.60
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		2 Parkinson's papers of 1320.85
pathways
Reactome		10 pathways; mostly immune signalling0.90
proposal for GNAI1, translation score 0.61

Knock down and overexpress GNAI1 in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR 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.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
α-synuclein uptake and myelin basic protein output under oxidative stress
Rule-out
If neither arm moves IL-1β 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 GNAI1 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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.

Sealed predictions

  1. GNAI1 in dopamine neurons, braak+0.15 (p 0.701) → +0.32 (p 0.407)receipt 8217
  2. GNAI1 in oligodendrocytes, braak+0.68 (p 0.045) → +0.59 (p 0.095)receipt 8216

Swarm cases

receipt 8217: GNAI1 in dopamine neurons, braak

power
full sample +0.19 (p 0.444, n 18), 95% CI -0.30 to +0.60. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.19 (p 0.444, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.20 (p 0.424, n 18). could be the mix.
skeptic
leave-one-out range +0.09 to +0.30, sign flips 0; without severely affected donors +0.19 (p 0.444, n 18). fragile.
cell type
strongest in oligodendrocytes: +0.61 (p 0.0069, n 18) vs +0.19 in dopamine neurons. proposing oligodendrocytes.
axis
no measure beats "tracks Braak Lewy-body stage" for GNAI1 in dopamine neurons.

follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up GNAI1 · oligodendrocytes · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) +0.07 p 0.790 (needs p < 2.6e-4)

receipt 8216: GNAI1 in oligodendrocytes, braak

power
full sample +0.61 (p 0.0069, n 18), 95% CI +0.20 to +0.84. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for sex: +0.61 (p 0.0069, n 18). holds up.
composition
oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.73 (p 6.6e-4, n 18). not the mix.
skeptic
leave-one-out range +0.56 to +0.71, sign flips 0; without severely affected donors +0.61 (p 0.0069, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for GNAI1 in oligodendrocytes.

case closed: nothing better to follow up.

Receipts

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