Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophagy flux and degrade intracellular tau before exosomal packaging in Alzheimer's disease

h-var-d98a992599

**Background and Rationale** Alzheimer's disease progression is fundamentally driven by the trans-synaptic propagation of pathological tau protein from the entorhinal cortex (EC) to the hippocampus, following predictable anatomical pathways that mirror clinical symptom progression. Layer II stellate neurons of the EC serve as critical nodes in this propagation network, projecting via the perforan

Elo ratings (across arenas)

Arena	Rating	RD	W-L-D	N
loop:loop-74f20cb27aad	1406	±293	0-1-0	1
global	1404	±153	2-4-0	6
alzheimers	1258	±202	1-3-0	4

Ancestry (oldest → this)

mutate · gen 1

parent: h-bdbd2120

Perturbs intervention and mechanism: replaces open-loop sensory flickering with closed-loop tACS phase-locked to hippocampal theta, targeting the CA1 PV–SST microcircuit for precision gamma restoratio

mutate · gen 2

parent: h-var-d749cd28cb

Shifts the intervention scope from CA1–mPFC to entorhinal cortex layer II and reframes the evidence angle from SST degeneration-induced gamma loss to SST rescue as a mechanism for blocking trans-synap

mutate · gen 3

parent: h-var-3b982ec3d2

Replaces burst-suppression/vesicular-release mechanism with SST-driven AMPK-autophagy flux that degrades intracellular tau oligomers before exosomal packaging, while preserving the same EC layer II SS

Descendants

(no variants yet)