Multi-omic expression of the VEGF family relates to Alzheimer's disease across diverse populations

INTRODUCTION: The vascular endothelial growth factor (VEGF) signaling family plays a role in neurodegenerative diseases, including Alzheimer's disease (AD). Previous work has shown widespread effects of the members FLT1, FLT4, and VEGFB on AD outcomes. However, these analyses have focused within the non-Hispanic White (NHW) population. NETHODS: The goal of this study was to analyze the effects of the VEGF family in underrepresented populations, leveraging large and diverse bulk RNA sequencing and tandem mass tag–mass spectrometry (TMT-MS) proteomic data. Outcomes included measures of AD pathology and diagnosis. RESULTS: Within underrepresented populations, we replicated previously reported effects of FLT1 and FLT4, whereby higher protein abundance was observed in the AD brain and was associated with higher neuropathology burden. In stratified analyses, these associations were largely consistent across race and ethnicity. DISCUSSION: This multi-omic study on the role of the VEGF family in AD emphasizes the need for more representative studies focused on therapeutic targets for AD. Highlights: Vascular endothelial growth factor (VEGF) genes and proteins were quantified in four different brain regions. Samples included participants from four different populations. Previously observed effects were replicated in diverse populations. This study is the largest multi-omic study of the vascular endothelial growth factor (VEGF) genes among Alzheimer's disease (AD) participants from diverse populations.