Abnormal　amyloid　beta　(A　beta)　aggregation　is　a　key　factor　in　Alzheimer＇s　disease　(AD)　pathology.　Despite　efforts　to　develop　A　beta　aggregation　inhibitors,　efficient　screening　strategies　remain　limited.　Here,　we　initially　applied　structure-based　virtual　screening　to　target　A　beta　fibril　ends,　aiming　to　identify　compounds　that　could　effectively　combat　AD　neurodegeneration.　Using　this　approach,　we　screened　a　traditional　Chinese　medicine　library　with　thousands　of　compounds,　and　selected　high-scoring　hits　likely　to　inhibit　fibril　elongation　or　promote　fibril　depolymerization.　Forsythoside　A　emerged　as　the　most　potent　inhibitor,　effectively　reducing　A　beta　40　aggregation　and　disassembling　pre-formed　fibrils,　as　confirmed　through　biophysical　assays　and　surface　plasmon　resonance　analysis.　Chemical　kinetics　further　elucidated　its　inhibitory　mechanism.　In　Caenorhabditis　elegans,　forsythoside　A　alleviated　A　beta-induced　toxicity　and　extended　the　lifespan　of　the　AD　transgenic　models.　Further　virtual　screening　and　experimental　validation　using　a　CNS-penetrant　compound　library　confirmed　the　robustness　of　our　strategy.　Our　study　underscores　the　effectiveness　of　virtual　screening　in　the　identification　of　A　beta　aggregation　inhibitors　and　emphasizes　the　critical　significance　of　targeting　fibril　ends.