Connectomic-genetic signatures in the cerebral small vessel disease

Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well understood how primary and secondary damage interact to give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross...

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Detalles Bibliográficos
Autores: Gutiérrez-Zúñiga, Raquel, Diez, Ibai, Bueichekú, Elisenda, Kim, Chan-Mi|||0000-0001-5686-1668, Orwig, William, Montal, Victor|||0000-0002-5714-9282, Fuentes, Blanca|||0000-0002-0363-862X, Díez-Tejedor, Exuperio, Gutiérrez-Fernández, Maria, Sepulcre, Jorge|||0000-0002-4199-2304
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282281
Acceso en línea:https://ddd.uab.cat/record/282281
https://dx.doi.org/urn:doi:10.1016/j.nbd.2022.105671
Access Level:acceso abierto
Palabra clave:Small vessel disease
Grey matter
White matter
Neurodegeneration
Connectomics
Genetics
Graph Theory
Descripción
Sumario:Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well understood how primary and secondary damage interact to give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross-sectional and longitudinal connectomic approaches, we unveil the bidirectional nature of GM and WM changes, that is, primary cortical neurodegeneration that leads to secondary alterations in vascular border zones, and WM lesions that lead to secondary neurodegeneration in cortical projecting areas. We found this GM-WM interaction to be essential for executive cognitive performance. Moreover, we also observed that the interlocked degeneration of GM and WM over time associates with prototypical expression levels of genes potentially linked to SVD. Among these connectomic-genetic intersections, we found that the Androgen Receptor (AR) gene, is a particularly central candidate gene that might confer key vulnerability for brain lesion development in SVD. In conclusion, this study advances in the understanding of the bidirectional relationships between GM and WM lesions, primary and secondary vascular neurodegeneration, and sheds light on the genetic signatures of SVD.