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Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease
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 polym...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439194/ https://www.ncbi.nlm.nih.gov/pubmed/37596325 http://dx.doi.org/10.1038/s41598-023-39576-7 |
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author | Manso-Calderón, Raquel Cacabelos-Pérez, Purificación Sevillano-García, M. Dolores Herrero-Prieto, M. Elisa González-Sarmiento, Rogelio |
author_facet | Manso-Calderón, Raquel Cacabelos-Pérez, Purificación Sevillano-García, M. Dolores Herrero-Prieto, M. Elisa González-Sarmiento, Rogelio |
author_sort | Manso-Calderón, Raquel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10439194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104391942023-08-20 Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease Manso-Calderón, Raquel Cacabelos-Pérez, Purificación Sevillano-García, M. Dolores Herrero-Prieto, M. Elisa González-Sarmiento, Rogelio Sci Rep Article 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. Nature Publishing Group UK 2023-08-18 /pmc/articles/PMC10439194/ /pubmed/37596325 http://dx.doi.org/10.1038/s41598-023-39576-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Manso-Calderón, Raquel Cacabelos-Pérez, Purificación Sevillano-García, M. Dolores Herrero-Prieto, M. Elisa González-Sarmiento, Rogelio Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title | Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title_full | Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title_fullStr | Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title_full_unstemmed | Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title_short | Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease |
title_sort | analysis of endothelial gene polymorphisms in spanish patients with vascular dementia and alzheimer´s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439194/ https://www.ncbi.nlm.nih.gov/pubmed/37596325 http://dx.doi.org/10.1038/s41598-023-39576-7 |
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