Axonal damage and inflammation response are biological correlates of decline in small-world values: a cohort study in autosomal dominant Alzheimer's disease.

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae357
Lisa Vermunt, Courtney L Sutphen, Ellen Dicks, Diederick M de Leeuw, Ricardo F Allegri, Sarah B Berman, David M Cash, Jasmeer P Chhatwal, Carlos Cruchaga, Gregory S Day, Michael Ewers, Martin R Farlow, Nick C Fox, Bernardino Ghetti, Neill R Graff-Radford, Jason Hassenstab, Mathias Jucker, Celeste M Karch, Jens Kuhle, Christoph Laske, Johannes Levin, Colin L Masters, Eric McDade, Hiroshi Mori, John C Morris, Richard J Perrin, Oliver Preische, Peter R Schofield, Marc Suárez-Calvet, Chengjie Xiong, Philip Scheltens, Charlotte E Teunissen, Pieter Jelle Visser, Randall J Bateman, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Betty M Tijms
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Abstract

The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer's disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer's disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers (N = 219) and non-carriers (N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.

轴突损伤和炎症反应是小世界值下降的生物学相关因素:一项关于常染色体显性阿尔茨海默病的队列研究。
在人的一生中,大脑灰质会以协调的模式发展和衰退。灰质结构的这种共变模式可以量化为灰质网络,并通过磁共振成像进行测量。在阿尔茨海默病中,灰质网络的全局组织变得更加随机,这可以通过小世界系数的下降来捕捉。在阿尔茨海默病的各个临床阶段,小世界值的下降都与认知能力下降密切相关。导致小世界值下降的生物学机制仍然未知。脑脊液(CSF)蛋白生物标志物可用于研究人类的各种病理机制,并能提供有关衰退的洞察力。我们调查了显性遗传阿尔茨海默氏症网络观察研究中突变携带者(219 人)和非携带者(136 人)的 10 种 CSF 蛋白质与小世界系数之间的关系。淀粉样蛋白β、Tau、突触(突触体相关蛋白-25、神经粒蛋白)和神经元钙传感蛋白(Visinin-like protein-1)的异常比小世界系数的丧失早数年,而脑脊液中炎症标记物(几丁质酶-3样蛋白1)和轴突损伤标记物(神经丝光)水平的升高与小世界系数的降低同时发生。这表明轴突丢失和炎症在灰质网络结构变化中起着一定的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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