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To investigate the underlying mechanisms, we evaluated BCG in the PS19 mouse model of tauopathy. We found that BCG administration reduced hippocampal phospho\u2013tau and microgliosis while preserving neuronal markers.\n                  <jats:italic>In vivo<\/jats:italic>\n                  volumetric T2-MRI demonstrated attenuation of brain atrophy accompanied by increased glutamate\u2013weighted CEST\u2013MRI signals. Functionally, BCG-treated mice showed improved performance in the novel object recognition test (NORT), as well as improved body-weight maintenance and survival. Transcriptomic profiling of the hippocampus revealed near complete normalization of the PS19 disease-associated gene expression signature towards that of healthy controls. Flow cytometric profiling of brain myeloid populations demonstrated a reduction in activated resident microglia, but total microglia cells remain elevated. Moreover, an increase of the co-stimulatory marker CD80 on the recruited peripheral myeloid cells ensues following BCG treatment. Consistent with this shift in myeloid state, primary brain myeloid cells from BCG-treated mice also exhibited enhanced phagocytosis of FITC\u2013labeled tau fibrils and increased lactate production. Together, these findings indicate that BCG induces systemic and CNS myeloid cell reprogramming that limits neuroinflammation, enhances tau clearance, and rescues cognitive and neurodegenerative phenotypes in a tauopathy model. BCG is a safe, readily available therapy that merits consideration as a preventive agent against dementia.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One sentence summary<\/jats:title>\n                  <jats:p>BCG therapy prevents tauopathy in PS19 mouse model.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.12.724591","type":"posted-content","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:05:12Z","timestamp":1778893512000},"source":"Crossref","is-referenced-by-count":0,"title":["BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice"],"prefix":"10.64898","author":[{"given":"Somnath","family":"Shee","sequence":"first","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meixiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD"},{"name":"Dept. of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghraj Singh","family":"Baghel","sequence":"additional","affiliation":[{"name":"Dept. of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD"},{"name":"Dept. of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shichun","family":"Lun","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh K.","family":"Yadav","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirbhay N.","family":"Yadav","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos E.","family":"Ruiz-Gonzalez","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Nuermberger","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaver M.","family":"Bhujwalla","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA"},{"name":"Dept. of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara S.","family":"Slusher","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD"},{"name":"Dept. of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA"},{"name":"Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA"},{"name":"Department of Physiology, Pharmacology and Therapeutics Johns Hopkins University School of Medicine, Baltimore, MD, USA"},{"name":"Dept. of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip 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