Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

CSF1R

colony stimulating factor 1 receptor

translation score 0.63, read 2026-10-18; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.20 (overall 0.15)0.20
cell type
Human Protein Atlas		cell type enhanced in microglia (702 nCPM)1.00
chemistry
Open Targets		compounds already reach it: vatalanib, axatilimab, imc-cs4 +181.00
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		90 Parkinson's papers of 3,0020.41
pathways
Reactome		3 pathways; mostly immune signalling0.90
proposal for CSF1R, translation score 0.63

Knock down and overexpress CSF1R 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; existing compounds already reach the inhibition arm.
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 CSF1R 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. CSF1R in dopamine neurons, braak-0.23 (p 0.560) → +0.09 (p 0.820)receipt 2196
  2. CSF1R in microglia, braak-0.29 (p 0.449) → -0.15 (p 0.702)receipt 2195

Swarm cases

receipt 2196: CSF1R in dopamine neurons, braak

power
full sample -0.08 (p 0.741, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.07 (p 0.787, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.06 (p 0.820, n 18). could be the mix.
skeptic
leave-one-out range -0.17 to +0.04, sign flips 3; without severely affected donors -0.08 (p 0.741, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for CSF1R in dopamine neurons.

case closed: nothing better to follow up.

receipt 2195: CSF1R in microglia, braak

power
full sample -0.22 (p 0.389, n 18), 95% CI -0.62 to +0.28. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.21 (p 0.408, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.11 (p 0.677, n 18). could be the mix.
skeptic
leave-one-out range -0.34 to -0.11, sign flips 0; without severely affected donors -0.22 (p 0.389, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for CSF1R in microglia.

case closed: nothing better to follow up.

Receipts

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