Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

GRIN2A

glutamate ionotropic receptor NMDA type subunit 2A

translation score 0.61, read 2026-10-27; 3 sealed predictions, 0 held; 3 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.63 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced in brain excitatory neurons (786 nCPM)1.00
chemistry
Open Targets		compounds already reach it: indantadol, dextromethorphan, cns-5161 +271.00
trials
ClinicalTrials.gov		5 Parkinson's trials, 1 stopped0.84
literature
PubMed		17 Parkinson's papers of 6170.62
pathways
Reactome		7 pathways; mostly dopamine synapse1.00
proposal for GRIN2A, translation score 0.61

Knock down and overexpress GRIN2A in dopamine neurons; measure evoked dopamine release and dopamine transporter uptake 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; existing compounds already reach the inhibition arm.
Molecular readout
evoked dopamine release and dopamine transporter uptake
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 evoked dopamine release 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 GRIN2A in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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 0.61; 2026-10-25 0.61; 2026-10-24 0.61; 2026-10-23 0.61.

Sealed predictions

  1. GRIN2A in dopamine neurons, braak+0.04 (p 0.919) → +0.53 (p 0.143)receipt 0537
  2. GRIN2A in dopamine neurons, resiliencen/a → n/areceipt 0050
  3. GRIN2A in dopamine neurons, braakn/a → n/areceipt 0049

Swarm cases

receipt 0537: GRIN2A in dopamine neurons, braak

power
full sample +0.19 (p 0.460, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.11 (p 0.658, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.01 (p 0.983, n 18). could be the mix.
skeptic
leave-one-out range +0.09 to +0.34, sign flips 0; without severely affected donors +0.19 (p 0.460, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for GRIN2A in dopamine neurons.

case closed: nothing better to follow up.

receipt 0050: GRIN2A in dopamine neurons, resilience

cell type
GRIN2A is not measured in dopamine neurons; looking elsewhere.
cell type
no other cell group does better.
axis
no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for GRIN2A in dopamine neurons.

case closed: nothing better to follow up.

receipt 0049: GRIN2A in dopamine neurons, braak

cell type
GRIN2A is not measured in dopamine neurons; looking elsewhere.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for GRIN2A in dopamine neurons.

case closed: nothing better to follow up.

Receipts

loading the receipts