Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease
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-nucleot...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39576-7 |
| _version_ | 1797453110225928192 |
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| author | Raquel Manso-Calderón Purificación Cacabelos-Pérez M. Dolores Sevillano-García M. Elisa Herrero-Prieto Rogelio González-Sarmiento |
| author_facet | Raquel Manso-Calderón Purificación Cacabelos-Pérez M. Dolores Sevillano-García M. Elisa Herrero-Prieto Rogelio González-Sarmiento |
| author_sort | Raquel Manso-Calderón |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:18:11Z |
| format | Article |
| id | doaj.art-0b4939557d2a44afb2afe4b0e3d3aa45 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:18:11Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0b4939557d2a44afb2afe4b0e3d3aa452023-11-26T12:57:43ZengNature PortfolioScientific Reports2045-23222023-08-0113111110.1038/s41598-023-39576-7Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s diseaseRaquel Manso-Calderón0Purificación Cacabelos-Pérez1M. Dolores Sevillano-García2M. Elisa Herrero-Prieto3Rogelio González-Sarmiento4Department of Neurology, Complejo Asistencial Universitario de Salamanca (CAUSA)Department of Neurology, Complejo Asistencial Universitario de Salamanca (CAUSA)Department of Neurology, Complejo Asistencial Universitario de Salamanca (CAUSA)Division of Neurology, Department of Internal Medicine, Complejo Asistencial de ÁvilaInstituto de Investigación Biomédica de Salamanca (IBSAL), University of SalamancaAbstract 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.https://doi.org/10.1038/s41598-023-39576-7 |
| spellingShingle | Raquel Manso-Calderón Purificación Cacabelos-Pérez M. Dolores Sevillano-García M. Elisa Herrero-Prieto Rogelio González-Sarmiento Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-39576-7 |
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