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bioRxiv · 10.64898/2025.12.22.695923

Systemic administration of PD-L1 blocking antibodies leads to removal of senescent microglia

Androsova, Y.·Kertser, A.·Partney, H.·Nathansohn, B.·Ibraheem, A.·Abellanas, M. A.·Croese, T.·Salame, T. M.·Akiva, H.·Krizhanovsky, V.·Schwartz, M.
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Abstract

Senescent microglia develop during aging and Alzheimers disease (AD), driving chronic neuroinflammation. Here we hypothesized that the previously observed disease-modifying effects of PD-1/PD-L1 blockade occur through clearance of senescent microglia. Using CyTOF, we found that a single systemic anti-PD-L1 injection leads to rapid elimination of senescent microglia in 5xFAD and aged wild-type mice, independently of Fc effector function, while increasing homeostatic microglia. These findings suggest that immune rejuvenation via PD-L1 blockade promotes disease modification in AD through senescent-microglial elimination.

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Androsova, Y., Kertser, A., Partney, H., Nathansohn, B., Ibraheem, A., Abellanas, M. A., Croese, T., Salame, T. M., Akiva, H., Krizhanovsky, V., Schwartz, M.. 2025-12-24. Systemic administration of PD-L1 blocking antibodies leads to removal of senescent microglia. https://doi.org/10.64898/2025.12.22.695923

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