Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

PTAFR

platelet activating factor receptor

translation score 0.62, read 2026-10-27; 2 sealed predictions, 0 held; 2 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.00 from other evidence0.00
cell type
Human Protein Atlas		cell type enhanced, including microglia; strongest in neutrophils0.75
chemistry
Open Targets		compounds already reach it: minopafant, rupatadine1.00
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		2 Parkinson's papers of 1000.85
pathways
Reactome		5 pathways; mostly immune signalling0.90
proposal for PTAFR, translation score 0.62

Knock down and overexpress PTAFR 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 PTAFR 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. PTAFR in dopamine neurons, braak-0.11 (p 0.787) → -0.37 (p 0.323)receipt 12412
  2. PTAFR in microglia, braak+0.00 (p 1.000) → -0.44 (p 0.232)receipt 12411

Swarm cases

receipt 12412: PTAFR in dopamine neurons, braak

power
full sample -0.34 (p 0.170, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: -0.36 (p 0.137, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.50 (p 0.035, n 18). not the mix.
skeptic
leave-one-out range -0.50 to -0.26, sign flips 0; without severely affected donors -0.34 (p 0.170, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for PTAFR in dopamine neurons.

case closed: nothing better to follow up.

receipt 12411: PTAFR in microglia, 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: -0.14 (p 0.585, n 18). does not hold up.
composition
microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.11 (p 0.658, n 18). could be the mix.
skeptic
leave-one-out range -0.28 to -0.02, sign flips 0; without severely affected donors -0.14 (p 0.585, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for PTAFR in microglia.

case closed: nothing better to follow up.

Receipts

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