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. 2023 Apr:124:11-17.
doi: 10.1016/j.neurobiolaging.2023.01.002. Epub 2023 Jan 7.

Whole blood transcript and protein abundance of the vascular endothelial growth factor family relate to cognitive performance

Julia B Libby  1 , Mabel Seto  2 , Omair A Khan  3 , Dandan Liu  3 , Vlad Petyuk  4 , Nekesa C Oliver  5 , Min Ji Choi  5 , Marsalas Whitaker  5 , Khiry L Patterson  5 , Albert B Arul  5 , Katherine A Gifford  1 , Kaj Blennow  6 , Henrik Zetterberg  7 , Logan Dumitrescu  8 , Renã As Robinson  9 , Angela L Jefferson  1 , Timothy J Hohman  10
Affiliations

Whole blood transcript and protein abundance of the vascular endothelial growth factor family relate to cognitive performance

Julia B Libby et al. Neurobiol Aging. 2023 Apr.

Abstract

The vascular endothelial growth factor (VEGF) family of genes has been implicated in the clinical development of Alzheimer's Disease (AD). A previous study identified associations between gene expression of VEGF family members in the prefrontal cortex and cognitive performance and AD pathology. This study explored if those associations were also observed in the blood. Consistent with previous observations in brain tissue, higher blood gene expression of placental growth factor (PGF) was associated with a faster rate of memory decline (p=0.04). Higher protein abundance of FMS-related receptor tyrosine kinase 4 (FLT4) in blood was associated with biomarker levels indicative of lower amyloid and tau pathology, opposite the direction observed in brain. Also, higher gene expression of VEGFB in blood was associated with better baseline memory (p=0.008). Notably, we observed that higher gene expression of VEGFB in blood was associated with lower expression of VEGFB in the brain (r=-0.19, p=0.02). Together, these results suggest that the VEGFB, FLT4, and PGF alterations in the AD brain may be detectable in the blood compartment.

Keywords: Alzheimer's disease; Blood biomarkers; Mild Cognitive Impairment; VEGF.

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Conflict of interest statement

Conflicts of Interest

HZ has served at scientific advisory boards and/or as a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red Abbey Labs, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all outside the work presented in this paper). TH is a member of the scientific advisory board for Vivid Genomics (also outside the work presented herein).

Figures

Figure 1.
Figure 1.. VEGFB and PGF Whole Blood Expression Association with Baseline and Longitudinal Changes in Memory
Whole blood expression of VEGFB (A) was associated with better memory performance in baseline analyses (β=0.48, p=0.0075). Whole blood expression of PGF (B) was associated with more rapid decline in memory (β=−0.02, p=0.04).
Figure 2.
Figure 2.. FLT4 Whole Blood Protein Abundance Associations with AD CSF Biomarkers
Whole blood protein abundance of FLT4 was associated with higher CSF levels of Aβ−42 (A, (β=41.34, p=0.042), lower CSF levels of tau (B, β=−57.34, p=0.002), and lower levels of phosphorylated tau (C, β=−6.34, p=0.003).
Figure 3.
Figure 3.. Correlation Between VEGFB Expression in Whole Blood and Brain Regions in GTEx
Pearson correlations were calculated between VEGFB expression in various brain regions and whole blood within GTEx (A). The most significant correlation was between expression in the prefrontal cortex and whole blood, indicated by the arrow (A). Higher levels of VEGFB expression in whole blood were associated with lower levels of VEGFB expression in the prefrontal cortex (B). No other significant correlations were observed.
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