Why have anti-Aβ clinical trials failed despite the established role of Aβ in AD pathogenesis?
Analysis ID: SDA-2026-04-16-gap-pubmed-20260410-180503-a7a03974 | Domain: neurodegeneration | Status: completed | Created: 2026-04-16T10:35:49.093065
Knowledge Graph: 2 edges — View JSON
Top Hypotheses (2 total)
#1 Complement-SASP Amplification Cascade as Mechanistic Link
0.608
C1QA, C1QB, C3, IL1B, NFKB1
Senescent microglia release SASP factors that amplify complement cascade activation (C1Q, C3), driving excessive synaptic pruning. This creates a feedforward loop where Aβ drives senescence, SASP ampl
#2 TREM2 Agonism to Restore Microglial Phagocytosis Across Both Pathologies
0.602
TREM2, TYROBP (DAP12), PLCG2, SYK
# TREM2 Agonism to Restore Microglial Phagocytosis Across Both Pathologies
## Hypothesis Overview
The progressive nature of Alzheimer's disease (AD) is driven not by a single pathological entity but