Astrocyte autophagy-pyroptosis crosstalk in Alzheimer’s: insights from knowledge graphs

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Abstract
Astrocytes play a crucial role in brain health and are implicated in various aspects of Alzheimer’s disease (AD) progression. However, the mechanism underlying astrocyte autophagy and pyroptosis in AD remains unclear. To advance this knowledge, we constructed a knowledge graph of AD and dementia (AdDKG) by integrating literature-derived data with the Systematized Nomenclature of Medicine – Clinical Terms (SNOMED CT). The core knowledge base, addkg , was created through named entity recognition and semantic annotation of 172 283 articles using a concept identifier (CI-er) tool. AdDKG knowledge graph extends addkg knowledge base by incorporating SNOMED CT to standardize entities and enrich their relations and attributes. To validate the usefulness of AdDKG, we designed a case study to investigate the roles of astrocyte autophagy and pyroptosis in AD. The query results demonstrated that AdDKG precisely retrieves and prioritizes highly relevant articles, enabling focused investigation of mechanistic relations that would otherwise require extensive manual curation. Further detailed analysis revealed that abnormal autophagy, pyroptosis-induced inflammation, and their interplay are pivotal in AD progression. These findings highlight the utility and efficiency of AdDKG as a research tool for AD research, through which we elucidated the autophagy-pyroptosis interaction in astrocytes as a critical AD mechanism.
Funding Information
  • Shanghai Pudong Municipal Health Commission (PWZbr 2022-09, 2025-PWXZ-08)
  • Shanghai Municipal Health Commission (PKJ2025-Y79)

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