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

Autor: Raquel Manso-Calderón, Purificación Cacabelos-Pérez, M. Dolores Sevillano-García, M. Elisa Herrero-Prieto, Rogelio González-Sarmiento
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-11 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-39576-7
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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