Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

• Published in: Scientific reports Vol. 13; no. 1; p. 13441
• Main Authors: Manso-Calderón, Raquel, Cacabelos-Pérez, Purificación, Sevillano-García, M. Dolores, Herrero-Prieto, M. Elisa, González-Sarmiento, Rogelio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/205; 631/337; 631/378; 692/308; 692/420; 692/617; 692/699/375/365/1283; Alzheimer's disease; Blood-brain barrier; Cerebral blood flow; Cognitive ability; Dementia; Dementia disorders; Gene polymorphism; Humanities and Social Sciences; multidisciplinary; Permeability; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Vascular dementia; Vascular diseases; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-39576-7

There is increasing evidence for the involvement of blood–brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated the association of four single-nucleotide polymorphisms ( VEGF , VEGFR2 and NOS3 ) with diagnosis and rate of cognitive decline in AD and VaD in a Spanish case–control cohort (150 VaD, 147 AD and 150 controls). Participants carrying -604AA genotype in VEGFR2 (rs2071559) were less susceptible to VaD after multiple testing. Further analysis for VaD subtype revealed a significant difference between small-vessel VaD patients and controls, but not for large-vessel VaD patients. In addition, -2578A and -460C alleles in VEGF (rs699947 and rs833061) showed to decrease the risk of AD, whereas NOS3 (rs1799983) influenced disease progression. Our study supports previous findings of a deleterious effect of VEGFR2 reduced expression on small-vessel disease, but not on large-vessel disease; as well as a detrimental effect of down-regulating VEGF and eNOS in AD, affecting vascular permeability and neuronal survival. These data highlight the relevance of endothelial function and, therefore, BBB in both VaD and AD.