Connectomic-genetic signatures in the cerebral small vessel disease
Gutiérrez-Zúñiga, Raquel (Hospital Universitario La Paz (Madrid))
Diez, Ibai (Harvard Medical School)
Bueichekú, Elisenda (Harvard Medical School)
Kim, Chan-Mi (Harvard Medical School)
Orwig, William (Harvard Medical School)
Montal, Victor (Institut d'Investigació Biomèdica Sant Pau)
Fuentes, Blanca (Hospital Universitario La Paz (Madrid))
Díez-Tejedor, Exuperio (Hospital Universitario La Paz (Madrid))
Gutiérrez-Fernández, Maria (Hospital Universitario La Paz (Madrid))
Sepulcre, Jorge (Harvard Medical School)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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.
Grants:	Instituto de Salud Carlos III CM18/00175
Note:	Altres ajuts: National Institutes of Health (NIH; R01AG061811, R01AG061445).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Small vessel disease ; Grey matter ; White matter ; Neurodegeneration ; Connectomics ; Genetics ; Graph Theory
Published in:	Neurobiology of Disease, Vol. 167 (january 2022) , p. 105671, ISSN 1095-953X

DOI: 10.1016/j.nbd.2022.105671
PMID: 35231560

10 p, 11.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles