Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

NBAS

NBAS subunit of NRZ tethering complex

translation score 0.58, read 2026-10-20; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.11 (overall 0.07)0.11
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		reachable by antibody0.45
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		no papers tie it to Parkinson's yet1.00
pathways
Reactome		1 pathway; mostly vesicle traffic1.00
proposal for NBAS, translation score 0.58

Knock down and overexpress NBAS in a dopamine neuron, astrocyte and microglia tri-culture; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
LRRK2 kinase activity (pT73-Rab10) and lysosome position
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
Rule-out
If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 NBAS in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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. NBAS in dopamine neurons, braak-0.06 (p 0.877) → +0.45 (p 0.230)receipt 4124

Swarm cases

receipt 4124: NBAS in dopamine neurons, braak

power
full sample +0.23 (p 0.365, n 18), 95% CI -0.27 to +0.63. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.19 (p 0.460, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.14 (p 0.567, n 18). could be the mix.
skeptic
leave-one-out range +0.11 to +0.35, sign flips 0; without severely affected donors +0.23 (p 0.365, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for NBAS in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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