Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

TLR10

toll like receptor 10

translation score 0.60, read 2026-10-22; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.03 from other evidence0.00
cell type
Human Protein Atlas		group enriched in microglia (92 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		1 Parkinson's papers of 3990.91
pathways
Reactome		3 pathways; mostly immune signalling0.90
proposal for TLR10, translation score 0.60

Knock down and overexpress TLR10 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 TLR10 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. TLR10 in dopamine neurons, braak-0.02 (p 0.964) → -0.50 (p 0.172)receipt 6883
  2. TLR10 in microglia, braak-0.48 (p 0.186) → -0.69 (p 0.042)receipt 6882

Swarm cases

receipt 6883: TLR10 in dopamine neurons, braak

power
full sample -0.14 (p 0.585, n 18), 95% CI -0.57 to +0.35. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.15 (p 0.555, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.31 (p 0.207, n 18). could be the mix.
skeptic
leave-one-out range -0.27 to -0.04, sign flips 0; without severely affected donors -0.14 (p 0.585, n 18). fragile.
cell type
strongest in microglia: -0.61 (p 0.0069, n 18) vs -0.14 in dopamine neurons. proposing microglia.
axis
no measure beats "tracks Braak Lewy-body stage" for TLR10 in dopamine neurons.

follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up TLR10 · microglia · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.30 p 0.286 (needs p < 3.0e-4)

receipt 6882: TLR10 in microglia, braak

power
full sample -0.61 (p 0.0069, n 18), 95% CI -0.84 to -0.20. the interval excludes zero: something may be there, smaller than a half can see.
confounder
adjusted for sex: -0.61 (p 0.0069, n 18). holds up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.58 (p 0.013, n 18). not the mix.
skeptic
leave-one-out range -0.74 to -0.56, sign flips 0; without severely affected donors -0.61 (p 0.0069, n 18). robust.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TLR10 in microglia.

case closed: nothing better to follow up.

Receipts

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