This challenge targets the hypothesis: **Synaptic Vesicle Cycle Hijacking: Shared Convergent Mechanism for α-Synuclein (PD) and Tau (AD) Trans-synaptic Propagation** **Hypothesis Summary:** Convergence hypothesis: Both α-synuclein (SNCA) in Parkinson's disease and tau (MAPT) in Alzheimer's disease exploit the same synaptic vesicle cycle machinery for trans-synaptic propagation, making the vesicle trafficking pathway a shared therapeutic target. PD-specific mechanism: α-synuclein binds to synaptic vesicles (SYP, SV2A, SYNPR) at the presynaptic terminal, inducing conformational conversion of endogenous α-synuclein into β-sheet-rich oligomers. These oligomers traffic in both directio **Falsifiable Predictions:** 1. Pharmacological modulation of SNCA 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:** $126,000 USD (composite score 0.760) **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.