Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

TNFSF13B

TNF superfamily member 13b

translation score 0.56, read 2026-10-24; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		no genetic evidence; overall 0.02 from other evidence0.00
cell type
Human Protein Atlas		expressed broadly, no clear home in brain cells0.40
chemistry
Open Targets		compounds already reach it: tibulizumab, blisibimod, atacicept +40.90
trials
ClinicalTrials.gov		no Parkinson's trials on record: an open field1.00
literature
PubMed		2 Parkinson's papers of 2660.85
pathways
Reactome		4 pathways; mostly immune signalling0.90
proposal for TNFSF13B, translation score 0.56

Knock down and overexpress TNFSF13B in a dopamine neuron, astrocyte and microglia tri-culture; measure IL-1β and TNF release and surface HLA-DR and dopamine neuron survival after α-synuclein fibril challenge.

Cell type
a dopamine neuron, astrocyte and microglia tri-culture
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
dopamine neuron survival after α-synuclein fibril challenge
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 TNFSF13B in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. TNFSF13B in dopamine neurons, braak+0.36 (p 0.348) → +0.46 (p 0.209)receipt 8546

Swarm cases

receipt 8546: TNFSF13B in dopamine neurons, braak

power
full sample +0.36 (p 0.137, n 18), 95% CI -0.12 to +0.71. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.34 (p 0.164, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.48 (p 0.046, n 18). not the mix.
skeptic
leave-one-out range +0.28 to +0.54, sign flips 0; without severely affected donors +0.36 (p 0.137, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for TNFSF13B in dopamine neurons.

case closed: nothing better to follow up.

Receipts

loading the receipts