Alzheimer’s Disease (AD) is an age-related neurodegenerative disorder characterized by progres-sive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracer-ebroventricular (ICV) injection of low to moderate doses of STZ in adult male Wistar rats can re-produce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, the knowledge regarding the molecular aspects of the ICV-STZ model is still in-cipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on Mass spectrometry (MS). To achieve that, samples from pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differ-ential protein abundance, pathway, and network analysis was performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in early stages of Late-Onset Alzheimer’s Disease (LOAD) based on differen-tially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further inves-tigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.