This challenge targets the hypothesis: **Tau/MAP6 ratio as a master switch for microtubule dynamics plasticity** **Hypothesis Summary:** The relative abundance of tau versus MAP6 on individual microtubules determines the balance between stable and labile domains, creating a spatial code for where dynamic remodeling (axon guidance, branching) versus stable support (process integrity) occurs Prediction: Manipulating the tau:MAP6 expression ratio will shift the entire spectrum of neuronal plasticity phenotypes in a predictable dose-response manner **Falsifiable Predictions:** 1. Pharmacological modulation of MAPT will alter neurodegeneration 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:** $125,000 USD (composite score 0.750) **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.