Vermunt Lisa, Sutphen Courtney L, Dicks Ellen, de Leeuw Diederick M, Allegri Ricardo F, Berman Sarah B, Cash David M, Chhatwal Jasmeer P, Cruchaga Carlos, Day Gregory S, Ewers Michael, Farlow Martin R, Fox Nick C, Ghetti Bernardino, Graff-Radford Neill R, Hassenstab Jason, Jucker Mathias, Karch Celeste M, Kuhle Jens, Laske Christoph, Levin Johannes, Masters Colin L, McDade Eric, Mori Hiroshi, Morris John C, Perrin Richard J, Preische Oliver, Schofield Peter R, Suárez-Calvet Marc, Xiong Chengjie, Scheltens Philip, Teunissen Charlotte E, Visser Pieter Jelle, Bateman Randall J, Benzinger Tammie L S, Fagan Anne M, Gordon Brian A, Tijms Betty M
Alzheimer center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit, 1081 HZ Amsterdam, The Netherlands.
Neurochemistry Laboratory, Departmentt of Laboratory Medicine, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit, 1081 HZ Amsterdam, The Netherlands.
Brain Commun. 2024 Oct 9;6(5):fcae357. doi: 10.1093/braincomms/fcae357. eCollection 2024.
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 ( = 219) and non-carriers ( = 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.
大脑灰质在整个生命周期中以协调的模式发育和衰退。灰质结构的这种共变模式可以量化为灰质网络，其可以通过磁共振成像进行测量。在阿尔茨海默病中，灰质网络的整体组织变得更加随机，这通过小世界系数的下降得以体现。小世界值的这种下降与阿尔茨海默病临床各阶段的认知衰退密切相关。导致小世界值下降的生物学机制尚不清楚。脑脊液（CSF）蛋白质生物标志物可用于研究人类的多种病理机制，并能为衰退提供见解。我们在显性遗传阿尔茨海默病网络观察研究的突变携带者（n = 219）和非携带者（n = 136）中，研究了10种脑脊液蛋白质与小世界系数之间的关系。淀粉样β蛋白、 Tau蛋白、突触蛋白（突触体相关蛋白25、神经颗粒素）和神经元钙传感器蛋白（类视黄醇蛋白1）的异常在小世界系数丧失前数年就已出现，而脑脊液中炎症标志物（几丁质酶3样蛋白1）和轴突损伤标志物（神经丝轻链）水平的升高与小世界值的降低同时出现。这表明轴突损失和炎症在灰质结构网络变化中起作用。
