Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

FCGR2B

Fc gamma receptor IIb

translation score 0.63, read 2026-10-18; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.41 (overall 0.27)0.41
cell type
Human Protein Atlas		cell type enhanced outside the brain (cdc)0.10
chemistry
Open Targets		compounds already reach it: obexelimab0.81
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		1 Parkinson's papers of 3230.91
pathways
Reactome		2 pathways; mostly immune signalling0.90
proposal for FCGR2B, translation score 0.63

Knock down and overexpress FCGR2B in a dopamine neuron, astrocyte and microglia tri-culture; measure IL-1β and TNF release and surface HLA-DR 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; existing compounds already reach the inhibition arm.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
dopamine neuron survival after α-synuclein fibril challenge
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 FCGR2B in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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. FCGR2B in dopamine neurons, braak-0.11 (p 0.778) → +0.00 (p 1.000)receipt 1503

Swarm cases

receipt 1503: FCGR2B in dopamine neurons, braak

power
full sample -0.21 (p 0.408, n 18), 95% CI -0.61 to +0.29. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.15 (p 0.561, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.29 (p 0.235, n 18). could be the mix.
skeptic
leave-one-out range -0.35 to -0.11, sign flips 0; without severely affected donors -0.21 (p 0.408, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for FCGR2B in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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