Carprofen alleviates Alzheimer-like phenotypes of 5XFAD transgenic mice by targeting the pathological hallmarks induced by amyloid-& beta; aggregation

Alzheimer's disease (AD) is characterized by misfolding, oligomerization, and accumulation of amyloid-& beta; (A & beta;) peptides in the brain. A & beta; monomers transform into A & beta; 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 A & beta; 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 A & beta; aggregating into fibrils and increases A & beta; plaques when intraperitoneally injected to 5XFAD transgenic mouse model. However, the drug seems to alleviate the key Alzheimer-like phenotypes induced by A & beta; 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 A & beta;(1-42)-infused mouse model. Collectively, while carprofen accelerates the conversion of A & beta; monomers into fibrils in vitro, the drug ameliorates the major pathological hallmarks of AD in vivo.

Automated summary

Alzheimer's disease is characterized by accumulation of Aβ peptides in the brain, which lead to cognitive dysfunctions. Carprofen, a non-steroidal anti-inflammatory drug, accelerates the formation of Aβ plaques, but also alleviates the pathological features of AD, including neuroinflammation and impaired memory.