Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

LILRB4

leukocyte immunoglobulin like receptor B4

translation score 0.59, read 2026-10-21; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets
no genetic evidence; overall 0.04 from other evidence0.00
cell type
Human Protein Atlas
cell type enriched in microglia (139 nCPM)1.00
chemistry
Open Targets
reachable by antibody0.45
trials
ClinicalTrials.gov
no Parkinson's trials on record: an open field1.00
literature
PubMed
2 Parkinson's papers of 1710.85
pathways
Reactome
1 pathway; mostly immune signalling0.90
proposal for LILRB4, translation score 0.59

Knock down and overexpress LILRB4 in microglia; measure IL-1β and TNF release and surface HLA-DR and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).

Cell type
microglia
Direction
Both arms: public data does not say which way helps.
Molecular readout
IL-1β and TNF release and surface HLA-DR
Functional readout
uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
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 LILRB4 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. LILRB4 in dopamine neurons, braak+0.09 (p 0.820) → -0.39 (p 0.300)receipt 5628
  2. LILRB4 in microglia, braak-0.58 (p 0.103) → -0.37 (p 0.329)receipt 5627

Swarm cases

receipt 5628: LILRB4 in dopamine neurons, braak

power
full sample -0.12 (p 0.633, n 18), 95% CI -0.56 to +0.37. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.13 (p 0.597, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.21 (p 0.393, n 18). could be the mix.
skeptic
leave-one-out range -0.24 to -0.01, sign flips 0; without severely affected donors -0.12 (p 0.633, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LILRB4 in dopamine neurons.

case closed: nothing better to follow up.

receipt 5627: LILRB4 in microglia, braak

power
full sample -0.24 (p 0.328, n 18), 95% CI -0.64 to +0.25. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.23 (p 0.351, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.12 (p 0.646, n 18). could be the mix.
skeptic
leave-one-out range -0.34 to -0.13, sign flips 0; without severely affected donors -0.24 (p 0.328, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LILRB4 in microglia.

case closed: nothing better to follow up.

Receipts

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