This challenge targets the hypothesis: **Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical memory circuits** **Hypothesis Summary:** ## Mechanistic Overview Alpha-gamma cross-frequency coupling enhancement to restore thalamo-cortical memory circuits starts from the claim that modulating SST within the disease context of Alzheimer's disease can redirect a disease-relevant process. The original description reads: "## **Molecular Mechanism and Rationale** The therapeutic strategy centers on restoring alpha-gamma cross-frequency coupling through targeted modulation of somatostatin-positive (SST+) GABAergic interneurons, which ser **Falsifiable Predictions:** 1. Pharmacological modulation of SST will alter Alzheimer's disease markers in validated models by ≥20% 2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems 3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%) 4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30% **Bounty Tier:** $127,482 USD (composite score 0.775) **Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis **Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.