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Libby JB, Seto M, Khan OA, Liu D, Petyuk V, Oliver NC, Choi MJ, Whitaker M, Patterson KL, Arul AB, Gifford KA, Blennow K, Zetterberg H, Dumitrescu L, Robinson RA, Jefferson AL, Hohman TJ. Whole blood transcript and protein abundance of the vascular endothelial growth factor family relate to cognitive performance. Neurobiology of aging. 2023 Apr;124(124). 11-17. NIHMSID: NIHMS1870676.
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.