Neurogenetic traits outline vulnerability to cortical disruption in Parkinson's disease.
Neurogenetic traits outline vulnerability to cortical disruption in Parkinson's disease.
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神经遗传特征概述了帕金森氏病皮质破坏的脆弱性。
DOI：
10.1016/j.nicl.2022.102941
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Sepulcre J
中科院分区：
文献类型：
--
作者：
Basaia S;Agosta F;Diez I;Bueichekú E;d'Oleire Uquillas F;Delgado-Alvarado M;Caballero-Gaudes C;Rodriguez-Oroz M;Stojkovic T;Kostic VS;Filippi M;Sepulcre J
在这项研究中，我们表征了α-突触核蛋白病理在体内的大规模传播途径，并确定了PD患者在不同疾病阶段的功能连接中断的不同模式。我们的研究结果确定了大规模PD病理的关键遗传特征，突出了它们对局灶性神经元对疾病进展的易感性的贡献。我们的研究结果为更好地解释PD病理不同空间脆弱性的大脑网络复杂性和机制铺平了道路，从而为早期诊断和未来的新治疗策略提供了信息。帕金森病（PD）中特定脑回路中神经元损伤易感性的遗传特征仍有待阐明。在这项研究中，我们描述了对照组和PD参与者的传播连接网络与人类皮层的基因表达模式（如SNCA基因）之间的脑拓扑交叉。我们观察到，脑连接起源于pd相关的脑干病理中心，再现了死后数据中α -突触核蛋白组织病理学的解剖分布。我们还发现，与pd相关病理的皮层繁殖模式最相关的基因集主要涉及微管细胞成分。因此，本研究揭示了通过评估人类大脑的体内连接轨迹和成功整合神经成像-遗传策略来增强PD神经元易感性检测的新途径。
In this study we characterized in vivo large-scale propagation pathways of α-synuclein pathology and identified different patterns of functional connectivity disruptions in PD patients at different stages of the disease. Our results identified key genetic signatures of large-scale PD pathology, highlighting their contribution to focal neuronal vulnerability to disease progression. Our results pave the way toward better accounting for the brain networks complexity and mechanisms underlying distinct spatial vulnerability to PD pathology, thus informing early diagnosis and future novel therapeutic strategies. The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson’s disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex – such as the SNCA gene. We observed that brain connectivity originated from PD-related pathology epicenters in the brainstem recapitulated the anatomical distribution of alpha-synuclein histopathology in postmortem data. We also discovered that the gene set most related to cortical propagation patterns of PD-related pathology was primarily involved in microtubule cellular components. Thus, this study sheds light on new avenues for enhancing detection of PD neuronal vulnerability via an evaluation of in vivo connectivity trajectories across the human brain and successful integration of neuroimaging-genetic strategies.
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影响因子：
4.3
作者：
Achard S;Bullmore E
通讯作者：
Bullmore E
影响因子：
4.8
作者：
Canu, Elisa;Agosta, Federica;Filippi, Massimo
通讯作者：
Filippi, Massimo
影响因子：
5.7
作者：
Baudrexel, Simon;Witte, Torsten;Hilker, Ruediger
通讯作者：
Hilker, Ruediger
DOI：
10.1093/brain/awu132
发表时间：
2014-08
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Crossley NA;Mechelli A;Scott J;Carletti F;Fox PT;McGuire P;Bullmore ET
通讯作者：
Bullmore ET
影响因子：
9.9
作者：
Campbell, Meghan C.;Koller, Jonathan M.;Perlmutter, Joel S.
通讯作者：
Perlmutter, Joel S.