The latest scientific advancements have revealed previously unidentified genes correlated with the concurrent presence of vascular pathologies and Alzheimer's disease (AD). Yet, the biological functions and mechanisms underlying their contribution to the disease pathology remain to be elucidated. Animal models enabling efficient functional screenings are essential. In pursuit of this aim, we created transgenic adult zebrafish models to investigate the pathological effects of amyloid toxicity. We conducted transcriptome analyses in zebrafish models, integrated with and compared to single nucleus transcriptome datasets from multi-ethnic Alzheimer's disease (AD) cohorts. In this project, we integrated eight single cell dataset of zebrafish model with amyloid toxicity with 24 sex-age matched human AD and control single nucleus transcriptomics data. After filtering out the low-quality cells, we analyzed 177,771 cells distributed in 38 clusters that belongs to 11 different cell types. Following the differentially expressed gene analysis and GO/KEGG pathway analysis, we identified evolutionary conserved changes in VEGF signaling pathway. To investigate the role of VEGF signaling further, we treated zebrafish with the KDRL inhibitors and performed single cell transcriptome analyses. As a result of single cell sequencing of treated fish, we analyzed 22,713 cells in 14 assigned cell types. With this analysis, we hypothesized a previously unidentified crosstalk between brain and vasculature and performed histological and functional analyses. Our studies propose zebrafish as a useful model for transcriptional and functional investigation of the contribution of vascular cells to AD pathology.