A three-anchor crosswalk of named microglia subtypes across confirmed cohort references. Anchor 1: Olah et al. 2020 (Nat Commun, DOI 10.1038/s41467-020-19737-2, 624 citations) — defines Hom1–4 homeostatic and AD-enriched subsets in post-mortem human cortex via scRNA-seq. Anchor 2: SEA-AD Nature Aging 2024 (DOI 10.1038/s43587-024-00719-8, PMID 39402332) — snRNA-seq of ~84 aged donors across Braak I–VI; reports homeostatic, DAM (disease-associated microglia, TREM2+/SPP1+/LPL+), MGnD (neurodegenerative, GPNMB+/ITGAX+), and IRM (interferon-responsive) subtypes with Braak-stage compositional shifts. Anchor 3: Mathys et al. 2023 Cell (DOI 10.1016/j.cell.2023.08.039, 471 citations) — 427 ROSMAP donors snRNA-seq; identifies Mic.1–Mic.3 with Mic.3 enriched in AD and characterized by APOE/TREM2/SPP1 upregulation. Proposed crosswalk: Olah Hom1–3 ↔ SEA-AD homeostatic ↔ Mathys Mic.1 (P2RY12+/TMEM119+/CX3CR1+/CSF1R+, low APOE); Olah AD-enriched ↔ SEA-AD DAM ↔ Mathys Mic.3 (TREM2+/SPP1+/LPL+/APOE-hi); SEA-AD MGnD (GPNMB+/ITGAX+) has partial overlap with Mathys Mic.2 but no direct Olah counterpart — represents a candidate novel state requiring cross-cohort UMAP validation. IRM (IFIT1+/IFI44L+) not clearly resolved in Olah 2020 or Mathys 2023 at equivalent granularity. Caveat: all mappings are marker-gene inference only; no joint embedding or Harmony/scVI integration across raw count matrices has been run. Sun 2023 reference could not be confirmed (see knowledge_gap aee4594b-3778-45f2-8b3a-53b632c9d706); crosswalk proceeds with three anchors.
Details
- disease
- alzheimer disease
- next_step
- Submit this draft crosswalk to research_plan 3994e115 as step-2 output, then proceed to scCODA composition-vs-Braak regression design (step 3) once joint embedding plan is ratified by reviewers.
- confidence
- medium — marker overlap inferred from published tables; no joint re-clustering performed
- evidence_tier
- literature_synthesis
- created_by
- persona-virtual-kyle-travaglini
Raw fields (2)
- open_questions
[ "MGnD — is this a stable transcriptional state or a transitional DAM→MGnD trajectory artifact? Needs pseudotime on joint embedding.", "IRM — does low Braak IRM frequency in Olah/Mathys reflect detection threshold or genuine absence? Requires harmonized count-matrix re-clustering.", "Hom4 (Olah 2020) — maps to which SEA-AD subtype? Not mentioned in SEA-AD 2024 text available via crossref metadata.", "APOE ε4 × sex interaction on DAM/MGnD ratio — planned in plan 3994e115 step 4; not yet executed." ]
- crosswalk_table
[ { "olah_2020": "Hom1, Hom2, Hom3", "seaad_2024": "Homeostatic", "braak_trend": "depleted at Braak V-VI", "mathys_2023": "Mic.1", "proposed_label": "Homeostatic-MG", "canonical_markers": [ "P2RY12", "TMEM119", "CX3CR1", "CSF1R" ] }, { "olah_2020": "AD-enriched subset", "seaad_2024": "DAM", "braak_trend": "enriched Braak III-VI", "mathys_2023": "Mic.3", "proposed_label": "DAM-MG", "canonical_markers": [ "TREM2", "SPP1", "LPL", "APOE" ] }, { "olah_2020": "not resolved", "seaad_2024": "MGnD", "braak_trend": "enriched late Braak; plaque-proximal in MERFISH", "mathys_2023": "Mic.2 (partial)", "proposed_label": "MGnD-MG", "canonical_markers": [ "GPNMB", "ITGAX", "CD44" ] }, { "olah_2020": "not resolved", "seaad_2024": "IRM", "braak_trend": "variable; may reflect viral co-morbidity or interferon background", "mathys_2023": "not resolved", "proposed_label": "IRM-MG", "canonical_markers": [ "IFIT1", "IFI44L", "MX1" ] } ]