| First Author | Lee D | Year | 2023 |
| Journal | Sci Rep | Volume | 13 |
| Issue | 1 | Pages | 10889 |
| PubMed ID | 37407605 | Mgi Jnum | J:337946 |
| Mgi Id | MGI:7508727 | Doi | 10.1038/s41598-023-36167-4 |
| Citation | Lee D, et al. (2023) Carprofen alleviates Alzheimer-like phenotypes of 5XFAD transgenic mice by targeting the pathological hallmarks induced by amyloid-beta aggregation. Sci Rep 13(1):10889 |
| abstractText | Alzheimer's disease (AD) is characterized by misfolding, oligomerization, and accumulation of amyloid-beta (Abeta) peptides in the brain. Abeta monomers transform into Abeta oligomers, which are toxic species, inducing tau hyperphosphorylation and the downstream effects on microglia and astrocytes, triggering synaptic and cognitive dysfunctions. The oligomers then deposit into Abeta plaques, primarily composed of beta-stranded fibrils, required for definitive AD diagnosis. As amyloid burden plays the pivotal role in AD pathogenesis, many efforts are devoted in preventing amyloidosis as a therapeutic approach to impede the disease progression. Here, we discovered carprofen, a non-steroidal anti-inflammatory drug, accelerates Abeta aggregating into fibrils and increases Abeta plaques when intraperitoneally injected to 5XFAD transgenic mouse model. However, the drug seems to alleviate the key Alzheimer-like phenotypes induced by Abeta aggregation as we found attenuated neuroinflammation, improved post-synaptic density expression, associated with synaptic plasticity, and decreased phosphorylated tau levels. Carprofen also rescued impaired working memory as we discovered improved spontaneous alternation performance through Y-maze test assessed with Abeta(1-42)-infused mouse model. Collectively, while carprofen accelerates the conversion of Abeta monomers into fibrils in vitro, the drug ameliorates the major pathological hallmarks of AD in vivo. |
