New candidate blood biomarkers potentially associated with white matter hyperintensities progression
We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50–70, who underwent two magnetic resonance imaging...
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| Published in | Scientific reports Vol. 11; no. 1; pp. 14324 - 10 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
12.07.2021
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2045-2322 2045-2322 |
| DOI | 10.1038/s41598-021-93498-w |
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| Abstract | We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50–70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies. |
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| AbstractList | Abstract We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50–70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies. We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50–70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies. We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies. |
| ArticleNumber | 14324 |
| Author | Penalba, Anna Pizarro, Jesús Hernández-Guillamon, Mar Riba-Llena, Iolanda Palà, Elena Jiménez-Balado, Joan Montaner, Joan Delgado, Pilar Faura, Júlia |
| Author_xml | – sequence: 1 givenname: Joan surname: Jiménez-Balado fullname: Jiménez-Balado, Joan organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 2 givenname: Jesús surname: Pizarro fullname: Pizarro, Jesús organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 3 givenname: Iolanda surname: Riba-Llena fullname: Riba-Llena, Iolanda organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 4 givenname: Anna surname: Penalba fullname: Penalba, Anna organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 5 givenname: Júlia surname: Faura fullname: Faura, Júlia organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 6 givenname: Elena surname: Palà fullname: Palà, Elena organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 7 givenname: Joan surname: Montaner fullname: Montaner, Joan organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània, Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena – sequence: 8 givenname: Mar surname: Hernández-Guillamon fullname: Hernández-Guillamon, Mar organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània – sequence: 9 givenname: Pilar surname: Delgado fullname: Delgado, Pilar email: pilar.delgado@vhir.org organization: Neurovascular Research Lab. Vall D’Hebron Research Institute, Universitat Autònoma de Barcelona, Edifici Mediterrània, Vall D’Hebron University Hospital, Universitat Autònoma de Barcelona, Dementia Unit, Neurology Service |
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| CitedBy_id | crossref_primary_10_3390_brainsci14030269 crossref_primary_10_1016_j_mri_2024_110213 crossref_primary_10_3390_cimb46010060 crossref_primary_10_3390_biology12010033 crossref_primary_10_1016_j_neurobiolaging_2023_05_012 |
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| Title | New candidate blood biomarkers potentially associated with white matter hyperintensities progression |
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