sex-divergent microglial activation states and X-linked immune escape genes should produce a measurable proximal phenotype before late disease pathology. The decisive test is sex-stratified single-nucleus RNA-seq with amyloid/tau pathology labels and longitudinal cognition models.
Curated pathway from expert analysis
flowchart TD
A["X-Linked Immune Genes<br/>MSEC and Other X-chromosome Escape Genes"]
B["Sex-Divergent Microglial States<br/>DAM1 vs DAM2 Polarization Shift"]
C["Amyloid Pathology Response<br/>Female Microglia More Inflammatory"]
D["Tau Pathology Spread<br/>Microglial Pruning of Tau+ Neurons"]
E["Sex-Specific Cognitive Decline Trajectory<br/>Females Faster Decline Post-Menopause"]
F["AD Progression<br/>Sex as Biological Variable in Disease Course"]
A --> B
B --> C
B --> D
C --> E
D --> E
E --> F
style A fill:#4a148c,stroke:#ce93d8,color:#ce93d8
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for AMYLOID-BETA yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for amyloid-beta.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No resource usage or linked notebooks recorded for this hypothesis yet.