Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

LILRB2

leukocyte immunoglobulin like receptor B2

translation score 0.58, read 2026-10-26; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.01 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced, including microglia; strongest in monocytes0.75
chemistry
Open Targets		a small-molecule pocket0.60
trials
ClinicalTrials.gov		2 Parkinson's trials, 0 stopped1.00
literature
PubMed		1 Parkinson's papers of 2260.91
pathways
Reactome		2 pathways; mostly immune signalling0.90
proposal for LILRB2, translation score 0.58

Knock down and overexpress LILRB2 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 LILRB2 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. LILRB2 in dopamine neurons, braak-0.62 (p 0.073) → -0.50 (p 0.167)receipt 11024
  2. LILRB2 in microglia, braak+0.20 (p 0.599) → -0.26 (p 0.507)receipt 11023

Swarm cases

receipt 11024: LILRB2 in dopamine neurons, braak

power
full sample -0.54 (p 0.019, n 18), 95% CI -0.81 to -0.10. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for sex: -0.52 (p 0.027, n 18). holds up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.76 (p 2.2e-4, n 18). not the mix.
skeptic
leave-one-out range -0.65 to -0.49, sign flips 0; without severely affected donors -0.54 (p 0.019, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LILRB2 in dopamine neurons.

case closed: nothing better to follow up.

receipt 11023: LILRB2 in microglia, braak

power
full sample +0.09 (p 0.709, n 18), 95% CI -0.39 to +0.54. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.08 (p 0.767, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.02 (p 0.942, n 18). could be the mix.
skeptic
leave-one-out range -0.04 to +0.25, sign flips 2; without severely affected donors +0.09 (p 0.709, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LILRB2 in microglia.

case closed: nothing better to follow up.

Receipts

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