Exercise improves cognitive function in Alzheimer’s disease via the CRNDE/miR-338-3p axis

Objectives Alzheimer’s disease (AD) is imposing a substantial burden on families. This study aimed to investigated the association between the lncRNA CRNDE/miR-338-3p axis, exercise-induced changes, and AD. Methods 100 AD patients and 100 healthy controls were recruited for the study. An AD mouse model was utilized. Both the human participants diagnosed with AD and the AD mice underwent an exercise intervention. The mRNA levels were quantified using RT-qPCR. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were assessed via enzyme-linked immunosorbent assay (ELISA). Cognitive function in the mice was evaluated using the Morris water maze (MWM) test. The interaction was validated through a dual-luciferase reporter assay. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were performed to elucidate the potentially related signaling pathways. Results CRNDE expression was significantly upregulated in AD. Exercise enhanced cognition and reduced inflammation in AD patients, concurrently lowering CRNDE levels. In vivo, experiments in AD mice confirmed that exercise exerted ameliorative effects on cognitive function and inflammatory response via downregulating CRNDE, but the influences were abolished by the miR-338-3p axis. GO analysis and KEGG pathway analysis further demonstrated that exercise influenced the CRNDE/miR-338-3p axis, which may be involved in the MAPK signaling pathway. Conclusions Exercise intervention could enhance the cognitive function of AD patients, and this effect was associated with the CRNDE/miR-338-3p axis.