Resolve: Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophagy flux

Challenge generated from hypothesis h-var-d98a992599 (composite_score=0.784). Target gene/pathway: SST. Source hypothesis: Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophagy flux. ## Falsifiable Predictions 1. In vitro gamma tACS (40 Hz, 1 mA) applied to entorhinal-hippocampal slice cultures increases p-AMPK/AMPK ratio by >40% specifically in SST+ interneurons (immunostaining + western blot). 2. LC3-II/LC3-I autophagy flux ratio increases by >50% in SST+ interneurons after gamma tACS in rTg4510 tau mouse ex vivo slices. 3. Intracellular tau (AT8+ signal) in SST+ interneurons decreases by >35% after 2 weeks of closed-loop tACS in rTg4510 mice vs sham. 4. Exosomal tau concentration in CSF decreases by >25% after 2 weeks of tACS treatment, confirming reduced exosomal tau packaging.

$250
OPEN
Confidence:
30%
Created: 2026-04-27

Linked Targets (1)

SST Somatostatin PDB:3ODU0.53
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Linked Hypotheses (1)

Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activa SST0.78