Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology.
Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology.
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DOI：
10.1371/journal.pbio.3001233
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发表时间：
2021-06
期刊：
影响因子：
9.8
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
--
作者：
Han F;Chen J;Belkin-Rosen A;Gu Y;Luo L;Buxton OM;Liu X;Alzheimer’s Disease Neuroimaging Initiative
淋巴系统在清除与阿尔茨海默病(AD)病理密切相关的淀粉样蛋白(Aβ，Aβ)和tau蛋白方面起着重要作用。淋巴清除以及Aβ的积累高度依赖于睡眠，但对淋巴流量至关重要的脑脊液运动背后的睡眠驱动力在很大程度上仍不清楚。最近的研究报道，在昏睡状态和睡眠中，广泛的、高幅度的自发脑激活，在静息状态下的功能磁共振成像(RsfMRI)中显示为大的全局信号峰，与脑脊液运动相结合，表明它们与淋巴流量和代谢物清除有潜在的联系。通过分析阿尔茨海默病神经成像计划的多模式数据，我们发现全球功能磁共振信号和脑脊液流入之间的耦合与AD相关的病理，包括AD的各种风险因素、AD相关疾病的严重性、皮质Aβ水平以及两年随访期间的认知功能下降。这些结果为睡眠依赖的全局脑活动以及相关的生理调节在清除与AD相关的脑废物中的参与提供了关键的初步证据。这项研究揭示了全球fMRI信号和脑脊液流入之间的强烈耦合，发现这与阿尔茨海默病相关的病理、疾病严重程度和认知能力下降有关。这支持了自发的低频脑动力学与阿尔茨海默病病理之间的联系，这可能是由于它们在淋巴清除中的作用。
The glymphatic system plays an important role in clearing the amyloid-β (Aβ) and tau proteins that are closely linked to Alzheimer disease (AD) pathology. Glymphatic clearance, as well as Aβ accumulation, is highly dependent on sleep, but the sleep-dependent driving forces behind cerebrospinal fluid (CSF) movements essential to the glymphatic flux remain largely unclear. Recent studies have reported that widespread, high-amplitude spontaneous brain activations in the drowsy state and during sleep, which are shown as large global signal peaks in resting-state functional magnetic resonance imaging (rsfMRI), are coupled with CSF movements, suggesting their potential link to glymphatic flux and metabolite clearance. By analyzing multimodal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project, here we showed that the coupling between the global fMRI signal and CSF influx is correlated with AD-related pathology, including various risk factors for AD, the severity of AD-related diseases, the cortical Aβ level, and cognitive decline over a 2-year follow-up. These results provide critical initial evidence for involvement of sleep-dependent global brain activity, as well as the associated physiological modulations, in the clearance of AD-related brain waste. This study reveals strong coupling between the global fMRI signal and cerebrospinal fluid influx, finding that this is correlated with Alzheimer’s disease-related pathology, disease severity, and cognitive decline. This supports a link between spontaneous low-frequency brain dynamics and Alzheimer’s disease pathology, presumably due to their role in glymphatic clearance.
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