The abnormal accumulation of copper ions (Cu2+) is considered to be one of the pathological factors of Alzheimer's disease (AD), but the internal relationship between Cu2+ and AD progression is still not fully clear. In this work, a sensitive and selective near-infrared fluorescent copper ion probe (DDP-Cu) was designed for quantification and visualization of Cu2+ level in lysates, living cells, living zebrafish and brain tissues of drosophila and mice with AD. By using this probe, we demonstrated that the content of Cu2+ in the brains of AD mice and drosophila enhanced nearly 3.5-fold and 4-fold than that of normal mice and drosophila, respectively. More importantly, pathogenesis analysis revealed that elevated Cu2+ led to changes in factors closely associated with AD, such as the increasing of reactive oxygen species(ROS), the aggregation of amyloid-β protein (Aβ) and nerve cell cytotoxicity. These findings could promote the understanding of the roles between Cu2+ and AD.