Vascular cognitive impairment, being a cerebrovascular condition that is more common in the aging population, results in a deterioration in cognitive capacities. Regarding these aspects, the identification of associated proteins, pathways, and treatment targets is crucial. The interactions that result in Vascular Cognitive Impairment can be better understood by looking into the interactors of the well-researched APP, which has been linked to dementia. Therefore, our study focused on identifying novel APP interactions by protein-protein interaction networks. After constructing the APP-centered dynamic-structural PPI network we investigated these interactions with PRISM. We suggested a number of interactions that could be relevant to VCI and found that APP binds more selectively to SORT1, MAPK8, and UBQLN1 proteins. Additionally, we propose that three mutations in the kinase DYRK1A (V165I, S337P, and D401G) may be essential for VCI through its interaction with APP.