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Now, in this study, we investigated the effect of chemotherapy on brain metastatic progression and promoting tumor\u2010mediated NFT. Results show chemotherapies increase brain\u2010barrier permeability and facilitate enhanced tumor infiltration, particularly through the blood\u2013cerebrospinal fluid barrier (BCSFB). This is attributed to increased expression of matrix metalloproteinase 9 (MMP9) which, in turn, mediates loss of Claudin\u20106 within the choroid plexus cells of the BCSFB. Importantly, increased MMP9 activity in the choroid epithelium following chemotherapy results in cleavage and release of Tau from breast cancer cells. This cleaved Tau forms tumor\u2010derived NFT that further destabilize the BCSFB. Our results underline for the first time the importance of the BCSFB as a vulnerable point of entry for brain\u2010seeking tumor cells post\u2010chemotherapy and indicate that tumor cells themselves contribute to Alzheimer's\u2010like tauopathy.<\/jats:p>","DOI":"10.1002\/jnr.25249","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T09:43:42Z","timestamp":1696326222000},"page":"1900-1913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Breast\u2010to\u2010brain metastasis is exacerbated with chemotherapy through blood\u2013cerebrospinal fluid barrier and induces Alzheimer's\u2010like pathology"],"prefix":"10.1002","volume":"101","author":[{"given":"B.","family":"Saatian","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Sedighi","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Eisenbarth","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Julian","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-3547","authenticated-orcid":false,"given":"V.","family":"Martirosian","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Keck School of Medicine University of Southern California  Los Angeles California USA"},{"name":"Brain Tumor Center University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lowman","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Engineering Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"LaViolette","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Engineering Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Remsik","sequence":"additional","affiliation":[{"name":"Department of Neurology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Boire","sequence":"additional","affiliation":[{"name":"Department of Neurology Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Sankey","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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