OSCR

BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice.

Overview

Authors: Somnath Shee1, Meixiang Huang2,3, Meghraj Singh Baghel4, Yuxin Zheng2,3, Shichun Lun1, Santosh K. Yadav5, Nirbhay N. Yadav5,6, Carlos E. Ruiz-Gonzalez1, Sandeep Tyagi1, Eric Nuermberger1, Sanjay K. Jain1, Zaver M. Bhujwalla5,7,8, Barbara S. Slusher2,3,9,10,11,12, Philip C. Wong4,12, William Bishai1
ORCID iDs: Somnath Shee, Meixiang Huang, Meghraj Singh Baghel, Yuxin Zheng, Nirbhay N. Yadav, Carlos E. Ruiz-Gonzalez, Eric Nuermberger, Sanjay K. Jain, Zaver M. Bhujwalla, Barbara S. Slusher, Philip C. Wong, William Bishai
  1. Center for Tuberculosis Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
  2. Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  4. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  5. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
  6. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
  7. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
  8. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  9. Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  10. Department of Physiology, Pharmacology and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  11. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  12. Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Institutions: Johns Hopkins University (United States); Johns Hopkins Medicine (United States); Kennedy Krieger Institute (United States); Sidney Kimmel Comprehensive Cancer Center (United States)
Journal: Science advances, volume 12, issue 43, article eaej4603
Dates: received 4 June 2026; accepted 17 September 2026; published online 21 October 2026; in print October 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1126/sciadv.aej4603 · PMID 42905846 · PMCID PMC13686014 · OpenAlex W7223101996
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: structural MRI / diffusion (modality), human (organism), mouse (organism), Alzheimer's / dementia (population)
Methods: Statistics, Smoothing, state filtering, decompositions, fMRI & imaging
MeSH: BCG Vaccine*, Cognition*, tau Proteins*, Tauopathies*, Animals, Disease Models, Animal, Hippocampus, Magnetic Resonance Imaging, Mice, Mice, Transgenic, Microglia, Vaccination (* major topic)
Journal subjects: Neuroscience, Diseases and Disorders
Topic: Alzheimer's disease research and treatments (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: national institutes of health (R01 AI155346, P30 CA006973, R01 CA281075, R01-AI190038, P30-AI168436)
Citations: not cited yet (Europe PMC); 97 references in the paper

Abstract

Retrospective studies in patients with nonmuscle invasive bladder cancer have reported a significant reduction in Alzheimer’s disease incidence (12 to 78%) among Bacille Calmette-Guérin (BCG) recipients versus controls. To investigate the underlying mechanisms, we evaluated BCG in the PS19 mouse model of tauopathy. We found that BCG administration reduced hippocampal phospho-tau and microgliosis while preserving neuronal markers. In vivo volumetric T2–magnetic resonance Imaging (MRI) demonstrated attenuation of brain atrophy accompanied by increased glutamate-weighted chemical exchange saturation transfer–MRI signals. Functionally, BCG-treated mice showed improved performance in the novel object recognition test, 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 toward 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 trained immunity 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 fluorescein isothiocyanate-labeled tau fibrils and increased lactate production. Together, these findings indicate that BCG induces systemic and central nervous system 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. Raw data generated during this study is provided with this paper as a separate Excel file labeled data S3. The RNA sequencing dataset is available on NCBI’s GEO (accession number: GSE326626; www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326626). No new materials were generated in this study.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 25 October 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 12 MeSH terms, 1 funder, 94 references.

Cite

This paper

Shee, S., Huang, M., Baghel, M. S., Zheng, Y., Lun, S., Yadav, S. K., Yadav, N. N., Ruiz-Gonzalez, C. E., Tyagi, S., Nuermberger, E., Jain, S. K., Bhujwalla, Z. M., Slusher, B. S., Wong, P. C., & Bishai, W. (2026). BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice. Science advances, 12(43), eaej4603. https://doi.org/10.1126/sciadv.aej4603

BibTeX

@article{shee2026bcg,
author = {Shee, Somnath and Huang, Meixiang and Baghel, Meghraj Singh and Zheng, Yuxin and Lun, Shichun and Yadav, Santosh K. and Yadav, Nirbhay N. and Ruiz-Gonzalez, Carlos E. and Tyagi, Sandeep and Nuermberger, Eric and Jain, Sanjay K. and Bhujwalla, Zaver M. and Slusher, Barbara S. and Wong, Philip C. and Bishai, William},
title = {{BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice}},
journal = {Science advances},
year = {2026},
month = oct,
volume = {12},
number = {43},
pages = {eaej4603},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aej4603},
url = {https://doi.org/10.1126/sciadv.aej4603},
pmid = {42905846},
pmcid = {PMC13686014}
}

RIS

TY - JOUR
AU - Shee, Somnath
AU - Huang, Meixiang
AU - Baghel, Meghraj Singh
AU - Zheng, Yuxin
AU - Lun, Shichun
AU - Yadav, Santosh K.
AU - Yadav, Nirbhay N.
AU - Ruiz-Gonzalez, Carlos E.
AU - Tyagi, Sandeep
AU - Nuermberger, Eric
AU - Jain, Sanjay K.
AU - Bhujwalla, Zaver M.
AU - Slusher, Barbara S.
AU - Wong, Philip C.
AU - Bishai, William
TI - BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/10/21
VL - 12
IS - 43
SP - eaej4603
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aej4603
UR - https://doi.org/10.1126/sciadv.aej4603
LA - en
ER -

CSL-JSON

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