New candidate blood biomarkers potentially associated with white matter hyperintensities progression
Jiménez-Balado, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pizarro Gonzálvez, Jesús (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Riba-Llena, Iolanda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Penalba, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Faura, Júlia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Palà, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Montaner, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández-Guillamon, Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Delgado Martínez, María Pilar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2021
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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017_FI_B 00064 Instituto de Salud Carlos III PI14/01535 Instituto de Salud Carlos III PI17/02222 Instituto de Salud Carlos III ICI14/307 Instituto de Salud Carlos III PI19/00217 Instituto de Salud Carlos III CP15/00010 Instituto de Salud Carlos III JR15/0003
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Neuroscience ; Blood-brain barrier ; Neuro-vascular interactions
Published in:	Scientific reports, Vol. 11 (july 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-93498-w
PMID: 34253757

10 p, 2.3 MB

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