Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

GAMT

guanidinoacetate N-methyltransferase

translation score 0.70, read 2026-10-17; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.70 (overall 0.43)0.70
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		a small-molecule pocket0.60
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		1 Parkinson's papers of 3620.91
pathways
Reactome		2 pathways; mostly energy0.60
proposal for GAMT, translation score 0.70

Knock down and overexpress GAMT in a dopamine neuron, astrocyte and microglia tri-culture; measure oxygen consumption rate and ATP output 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
oxygen consumption rate and ATP output
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
Rule-out
If neither arm moves oxygen consumption rate 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 GAMT in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. GAMT in dopamine neurons, braak+0.11 (p 0.775) → -0.47 (p 0.197)receipt 0481

Swarm cases

receipt 0481: GAMT in dopamine neurons, braak

power
full sample -0.05 (p 0.854, n 18), 95% CI -0.50 to +0.43. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.04 (p 0.867, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.00 (p 0.997, n 18). could be the mix.
skeptic
leave-one-out range -0.20 to +0.08, sign flips 5; without severely affected donors -0.05 (p 0.854, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for GAMT in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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