Connectomic-genetic signatures in the cerebral small vessel disease
Por:
Gutiérrez-Zúñiga R., Diez I., Bueichekú E., Kim C.-M., Orwig W., Montal V., Fuentes B., Díez-Tejedor E., Fernández M.G., Sepulcre J.
Publicada:
1 jun 2022
Ahead of Print:
1 mar 2022
Resumen:
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.
Filiaciones:
Gutiérrez-Zúñiga R.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Department of Neurology and Stroke Centre, Neurological Science and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain
Diez I.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States
Bueichekú E.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Kim C.-M.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Orwig W.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States
Montal V.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Fuentes B.:
Department of Neurology and Stroke Centre, Neurological Science and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain
Díez-Tejedor E.:
Department of Neurology and Stroke Centre, Neurological Science and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain
Fernández M.G.:
Department of Neurology and Stroke Centre, Neurological Science and Cerebrovascular Research Laboratory, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Universidad Autónoma de Madrid, Madrid, Spain
Sepulcre J.:
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States
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