Alzheimer's disease (AD) is an age-related neurodegenerative disease with unknown mechanism that is characterized by the aggregation of abnormal proteins and dysfunction of immune responses. In this study, an integrative approach employing in silico analysis and wet-lab experiment was conducted to estimate the degrees of innate immune system relevant gene expression, neurotoxic Aβ42 generation and neuronal apoptosis in normal Drosophila melanogaster and a transgenic model of AD. Results demonstrated mRNA levels of antimicrobial peptide (AMP) genes gradually increased with age in wild-type flies, while which exhibited a trend for an initial decrease followed by subsequent increase during aging in the AD group. Time series and correlation analysis illustrated indicated a potential relationship between variation in AMP expression and Aβ42 concentration. In conclusion, our study provides evidence for abnormal gene expression of AMPs in AD flies with age, which is distinct from the expression profiles in the normal aging process. Aberrant AMP expression may participate in the onset and development of AD by inducing or accelerating Aβ deposition. These findings suggest that AMPs may serve as potential diagnostic biomarkers and therapeutic targets. However, further studies are required to elucidate the pathological effects and underlying mechanisms of AMP dysregulation in AD progression.