The anti-inflammatory drug Montelukast ameliorates cognitive deficits by rescuing the inflammatory levels in young AD animal models

Neuroinflammation precedes the clinical symptoms onset of Alzheimer's disease (AD) by decades. However, the anti-inflammatory drugs were not always effective at all stages of the disease. Here, using the fly and mouse AD models, we evaluated the effects of anti-inflammatory drugs on inflammatory-related factors and the proinflammatory cytokines at different ages of AD animals. We also performed behavioral tests to evaluate the cognitive aspects of AD. Combined with the bioinformatics analysis, we would like to exhibit a better understanding of AD. Based on the previous studies and reanalysis of published database, we found aged AD animals might better represent the inflammatory status of symptomatic AD. Our results showed that mRNA levels of antimicrobial peptides (AMPs) were highly expressed in 10-day-old AD flies, while no significant difference was observed in 40-day-old AD. In aged APP/PS1 mice (22.5 months), inflammatory-related factors NF-κB, IBA1, and the mRNA levels of proinflammatory cytokines Il-1β and Il-6 were not differentially expressed. In contrast, a significant increase was observed in 7.5-month-old APP/PS1 mice. Moreover, the anti-inflammatory drug Montelukast (MON) did not ameliorate the inflammatory and cognitive defects in 22.5-month-old aged mice but showed a rescue effect in 7.5-month-old young APP/PS1 mice. Altogether, our study demonstrates the different inflammatory status might lead to variations of anti-inflammatory drug efficacy, which helps to clarify the importance of considering the pathological stage of the disease when administering treatment.