Morrissey Zachery D, Gao Jin, Zhan Liang, Li Weiguo, Fortel Igor, Saido Takaomi, Saito Takashi, Bakker Arnold, Mackin Scott, Ajilore Olusola, Lazarov Orly, Leow Alex D
Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, United States.
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States.
Front Aging Neurosci. 2023 Jan 12;14:1085989. doi: 10.3389/fnagi.2022.1085989. eCollection 2022.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD.
To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations ( knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age.
We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice.
Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病。然而，AD的早期过程尚未完全了解，可能在症状出现前数年就已开始。重要的是，包括海马体在内的默认模式网络的破坏与AD有关。
为了研究功能网络连通性变化在AD早期阶段的作用，我们使用了一种在雌性小鼠中携带三种家族性AD突变（敲入，APPKI）的小鼠模型，对幼年、中年和老年组进行静息态功能磁共振成像（rs-fMRI）。对海马体的半球间和半球内功能连通性（FC）进行跨年龄建模。
我们观察到海马体的半球间功能连通性（FC）在各年龄段都较高。然而，在老年的APPKI小鼠中，这种连通性降低了。此外，我们观察到APPKI小鼠的FC半球不对称性丧失。
总之，这表明在淀粉样β斑块大量出现之前，海马体FC就已经发生了早期变化，这可能作为AD的早期生物标志物具有临床相关性。
