Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

LAIR1

leukocyte associated immunoglobulin like receptor 1

translation score 0.62, 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 enriched in microglia (85 nCPM)1.00
chemistry
Open Targets		a small-molecule pocket0.60
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		1 Parkinson's papers of 2940.91
pathways
Reactome		2 pathways; mostly immune signalling0.90
proposal for LAIR1, translation score 0.62

Knock down and overexpress LAIR1 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 LAIR1 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. LAIR1 in microglia, braak-0.27 (p 0.487) → -0.72 (p 0.029)receipt 10419
  2. LAIR1 in dopamine neurons, braak-0.82 (p 0.007) → +0.35 (p 0.349)receipt 10420

Swarm cases

receipt 10420: LAIR1 in dopamine neurons, braak

power
full sample -0.27 (p 0.285, n 18), 95% CI -0.65 to +0.23. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.28 (p 0.265, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.32 (p 0.191, n 18). could be the mix.
skeptic
leave-one-out range -0.43 to -0.17, sign flips 0; without severely affected donors -0.27 (p 0.285, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LAIR1 in dopamine neurons.

case closed: nothing better to follow up.

receipt 10419: LAIR1 in microglia, braak

power
full sample -0.34 (p 0.161, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.34 (p 0.170, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.42 (p 0.082, n 18). could be the mix.
skeptic
leave-one-out range -0.46 to -0.27, sign flips 0; without severely affected donors -0.34 (p 0.161, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for LAIR1 in microglia.

case closed: nothing better to follow up.

Receipts

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