Donanemab triggers acute microglial activation (ARIA-E). Patients achieving favorable M2-like phenotype show better p-tau217 normalization due to enhanced tau aggregate clearance, while persistent M1 phenotype may show biomarker dissociation. However, TSPO-PET M1/M2 specificity in humans is questionable—human microglia do not conform cleanly to the rodent M1/M2 dichotomy, and TSPO signals are non-specific for activation state.
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.52
Evidence
0.45
Novelty
0.62
Feasibility
0.42
Impact
0.55
Druggability
0.45
Safety
0.58
Competition
0.75
Data
0.48
Reproducible
0.42
KG Connect
0.53
Score Breakdown
Dimension
Microglial Reactivation Status
Mechanistic
0.520
Evidence
0.450
Novelty
0.620
Feasibility
0.420
Impact
0.550
Druggability
0.450
Safety
0.580
Competition
0.750
Data
0.480
Reproducible
0.420
KG Connect
0.533
Evidence
Microglial Reactivation Status Modifies Amyloid Clearance an