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

**Authors:** Julia B. Libby, Kacie D. Deters, Nilüfer Ertekin‐Taner, Minerva M. Carrasquillo, Mariet Allen, Philip De Jager, Vilas Menon, Bin Zhang, Vahram Haroutunian, Allan I. Levey, Nicholas T. Seyfried, Rima Kaddurah‐Daouk, Steve Finkbeiner, Daifeng Wang, Anna K. Greenwood, Abby Vander Linden, Laura Heath, William L. Poehlman, Logan Dumitrescu, Vladislav A. Petyuk, David A. Bennett, Julie A. Schneider, Lisa L. Barnes, Timothy J. Hohman

PMC · DOI: 10.1002/alz.71100 · Alzheimer's & Dementia · 2026-01-28

## TL;DR

This study shows that VEGF family genes and proteins are linked to Alzheimer's disease in diverse populations, highlighting the importance of inclusive research.

## Contribution

This is the largest multi-omic study of VEGF genes in Alzheimer's disease across diverse populations.

## Key findings

- Higher protein abundance of FLT1 and FLT4 was observed in the AD brain.
- These associations were consistent across race and ethnicity in underrepresented populations.
- VEGF family effects were replicated in diverse populations using RNA and proteomic data.

## Abstract

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.

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.

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.

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.

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.

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.

## Linked entities

- **Genes:** FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321], FLT4 (fms related receptor tyrosine kinase 4) [NCBI Gene 2324], VEGFB (vascular endothelial growth factor B) [NCBI Gene 7423], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422]
- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** VEGFC (vascular endothelial growth factor C) [NCBI Gene 7424] {aka Flt4-L, LMPH1D, LMPHM4, VRP}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, C6orf15 (chromosome 6 open reading frame 15) [NCBI Gene 29113] {aka STG}, NRP2 (neuropilin 2) [NCBI Gene 8828] {aka NP2, NPN2, PRO2714, VEGF165R2}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, FLT4 (fms related receptor tyrosine kinase 4) [NCBI Gene 2324] {aka CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL}, VEGFB (vascular endothelial growth factor B) [NCBI Gene 7423] {aka VEGFL, VRF}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, NRP1 (neuropilin 1) [NCBI Gene 8829] {aka BDCA4, CD304, NP1, NRP, VEGF165R}, VEGFD (vascular endothelial growth factor D) [NCBI Gene 2277] {aka FIGF, VEGF-D}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}
- **Diseases:** neurodegeneration (MESH:D019636), stroke (MESH:D020521), Dementia (MESH:D003704), neuritic plaques (MESH:D058225), death (MESH:D003643), cognitively impaired (MESH:D003072), RESEARCH (MESH:D014947), AD (MESH:D000544), neuronal dysfunction (MESH:D009461), amyloid (MESH:C000718787), CNS diseases (MESH:D002493), Parkinson's disease (MESH:D010300), brain amyloidosis (MESH:D000686), brain injury (MESH:D001930)
- **Chemicals:** TP (-), AMP (MESH:D000249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12848908/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12848908/full.md

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Source: https://tomesphere.com/paper/PMC12848908