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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Detalles Bibliográficos
Autores: Jiménez-Balado, Joan|||0000-0003-4125-9134, Pizarro Gonzálvez, Jesús|||0000-0002-5808-9293, Riba Llena, Iolanda, Penalba, Anna, Faura, Júlia|||0000-0002-8436-1377, Palà, Elena|||0000-0002-1074-990X, Montaner, Joan|||0000-0003-4845-2279, Hernandez Guillamon, Maria Mar|||0000-0001-8844-0091, Delgado Martínez, María Pilar|||0000-0002-1628-4488
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:256503
Acceso en línea:https://ddd.uab.cat/record/256503
https://dx.doi.org/urn:doi:10.1038/s41598-021-93498-w
Access Level:acceso abierto
Palabra clave:Neuroscience
Blood-brain barrier
Neuro-vascular interactions
Descripción
Sumario: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.