CNSC-02. BREAST TO BRAIN METASTASIS IS EXACERBATED WITH CHEMOTHERAPY THROUGH BLOOD-CEREBRAL SPINAL FLUID-BARRIER AND INDUCES ALZHEIMER’S-LIKE PATHOLOGY

Abstract Control of breast to brain metastasis remains an urgent unmet clinical need. While chemotherapies are essential in reducing systemic tumor burden, they have also shown promote non-brain metastatic invasiveness and drug-driven neurocognitive deficits through formation neurofibrillary tangles (NFT) independently. Now, this study we investigated the effect chemotherapy on progression promoting tumor-mediated NFT. Results show increased brain-barrier permeability facilitate enhanced infiltration, particularly blood-cerebrospinal fluid-barrier (BCSFB). This is attributed expression matrix metalloproteinase 9 (MMP9) which, turn, mediates loss Claudin-6 within choroid plexus cells BCSFB. Importantly, MMP9 activity epithelium following results cleavage Tau released from cancer cells. cleaved forms tumor-derived NFT that further destabilize Our underline for first time importance BCSFB as a vulnerable point entry brain-seeking post-chemotherapy indicate themselves contribute Alzheimer’s-like tauopathy.