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{
  "disease": "alzheimer's disease",
  "summary": "Extract per-donor cell-type proportion estimates for microglia subtypes (homeostatic MG, DAM, MGnD/SPP1+GPNMB+) and oligodendrocyte lineage subtypes (Oligo-1, OPC) from SEA-AD snRNA-seq metadata and ROSMAP harmonized counts. Fit Dirichlet regression models with Braak stage (I-VI) as the predictor for each subtype independently. Identify the Braak inflection point (first stage at which posterior credible interval excludes zero change) for DAM/MGnD expansion versus Oligo/OPC depletion. Test whether the two inflection stages are statistically distinguishable using bootstrap confidence intervals. Secondary analysis: compute SPP1-CD44 and C1q-C3 ligand-receptor co-expression scores in spatially co-registered MERFISH data from SEA-AD, stratified by proximity to plaque masks.",
  "hypothesis": "DAM/MGnD microglia proportion increases at an earlier Braak inflection point than the Oligo-1/OPC proportion decline, indicating that neuroinflammatory microglial activation precedes oligodendrocyte loss in AD DLPFC.",
  "target_ref": "SEA-AD:snRNA-seq:DLPFC",
  "identification_strategy": "observational"
}