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

Yuliya Androsova, Alexander Kertser, Hannah Partney, Bar Nathansohn, Angham Ibraheem, Miguel Abellanas, Tommaso Croese, Tomer Meir Salame, Hagay Akiva, Valery Krizhanovsky, Michal Schwartz
2025 · doi:10.64898/2025.12.22.695923
preprint OA: closed
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Abstract

Senescent microglia develop during aging and Alzheimer’s 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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[{'doi': None, 'name': 'This study was supported by Thompson foundation a grant from the ERNA-NET (given to MS).', 'awards': []}]

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