SynthesisMolecular psychiatry2026
Potential beneficial effects of PD-1/PD-L1 blockade in Alzheimer's disease: a systematic review and meta-analysis of preclinical and clinical studies.
Synthesis in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Several methodological issues in the systematic review "PD-1/PD-L1 blockade in Alzheimer's disease".Molecular psychiatry · 2026Article
- Targeting the crosstalk between Alzheimer's disease and gastrointestinal cancers.Molecular medicine (Cambridge, Mass.) · 2026Review
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
backgroundProgrammed cell death protein 1 (PD-1) and its ligand (PD-L1) are crucial in cancer immune evasion and in modulating neuroinflammation. Although PD-1/PD-L1 signaling is believed to modulate immune and neuronal responses, its role in AD pathophysiology remains unclear, with existing studies reporting inconsistent findings.
methodThis systematic review and meta-analysis investigated the effects of PD-1/PD-L1 blockade on AD-related pathology and cognitive behavior in preclinical studies. Additionally, we evaluated the impact of PD-1/PD-L1 inhibitors on cognitive outcomes in clinical studies involving cancer patients. Relevant research was systematically identified using the MEDLINE, Embase, CENTRAL, and Web of Science databases from their inception until July 31, 2025. Overall, 40 studies were included in this meta-analysis, conducted using R software.
resultsPreclinical studies revealed that blockade of PD-1 signaling reduces amyloid-beta plaque burden, tau phosphorylation, and astrocyte reactivity in AD mouse models. These pathological improvements were accompanied by enhanced cognitive performance, whereas wild-type mice showed no significant cognitive changes under the same treatment, whereas wild-type mice showed no significant cognitive changes under the same treatment. Furthermore, clinical studies demonstrated the beneficial effect of PD-1 signaling inhibitors on cognitive function in patients with cancer.
conclusionsPD-1/PD-L1 inhibition impacts AD pathology and cognitive function, suggesting its potential as a therapeutic development strategy for AD. Further studies are warranted to clarify the exact mechanisms, opening avenues for future therapies that modulate the PD-1/PD-L1 pathway for AD.
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