Braak stage 1, 100% of pigmented neurons left
parkinsonconnecting

Gene record

CDH8

cadherin 8

translation score 0.58, read 2026-10-18; 1 sealed predictions, 0 held; 1 receipts.

Six readers

readerfoundscore
genetics
Open Targets		genetic association 0.21 (overall 0.13)0.21
cell type
Human Protein Atlas		cell type enhanced in brain inhibitory neurons (479 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		2 Parkinson's papers of 700.85
pathways
Reactome		2 pathways; mostly other0.30
proposal for CDH8, translation score 0.58

Knock down and overexpress CDH8 in dopamine neurons; measure a transcriptome-wide state shift (bulk RNA-seq) and survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils.

Cell type
dopamine neurons
Direction
Both arms: public data does not say which way helps.
Molecular readout
a transcriptome-wide state shift (bulk RNA-seq)
Functional readout
survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils
Rule-out
If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 CDH8 in iPSC-derived midbrain dopamine neurons (FOXA2+, LMX1A+, TH+); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); survival of TH-positive neurons and phospho-α-synuclein (pS129) inclusions after seeding with α-synuclein fibrils. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.

Sealed predictions

  1. CDH8 in dopamine neurons, braak-0.23 (p 0.549) → +0.58 (p 0.101)receipt 2289

Swarm cases

receipt 2289: CDH8 in dopamine neurons, braak

power
full sample +0.19 (p 0.450, n 18), 95% CI -0.30 to +0.60. the interval is wide: not enough donors to tell.
confounder
adjusted for sex: +0.16 (p 0.526, n 18). does not hold up.
composition
dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.526, n 18). could be the mix.
skeptic
leave-one-out range +0.09 to +0.32, sign flips 0; without severely affected donors +0.19 (p 0.450, n 18). fragile.
cell type
no other cell group does better.
axis
no measure beats "tracks Braak Lewy-body stage" for CDH8 in dopamine neurons.

case closed: nothing better to follow up.

Receipts

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