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{
  "disease": "alzheimer disease",
  "summary": "Apply cross-lineage Dirichlet regression and bootstrap inflection-point estimation to SEA-AD snRNA-seq subtype proportions (microglia: MG-homeostatic, MG-DAM, MG-MGnD; oligodendrocyte lineage: Oligo-1, Oligo-2, OPC) stratified by Braak stage I–VI. Primary output: per-lineage inflection Braak stage with 95% bootstrap CI, tested for ordering (H0: simultaneous onset). Secondary output: ligand-receptor co-expression score (SPP1–CD44, C1q–C3) in SEA-AD MERFISH data as a function of distance to nearest amyloid plaque mask. Replicate in ROSMAP (Mathys 2023). Success criterion: microglia inflection Braak stage strictly earlier than oligodendrocyte inflection Braak stage in both cohorts, p < 0.05 after Bonferroni correction.",
  "hypothesis": "DAM/MGnD microglia expansion precedes Oligo-1/OPC proportional decline across Braak stages in human DLPFC, consistent with microglia-to-oligodendrocyte signaling (SPP1–CD44, C1q–C3) as a driver rather than a consequence of white matter degeneration in AD.",
  "target_ref": "dataset:SEA-AD-snRNAseq",
  "identification_strategy": "observational"
}