Zhong Jiayi, Zhang Xiaochen, Xu Huanyu, Zheng Xiaoran, Wang Luyao, Jiang Jiehui, Li Yunxia
School of Life Science, Shanghai University, Shanghai, China.
Department of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Neurosci. 2023 Jul 21;17:1222857. doi: 10.3389/fnins.2023.1222857. eCollection 2023.
Alzheimer's disease (AD) is one of the world's well-known neurodegenerative diseases, which is related to the balance mechanism of production and clearance of two proteins (amyloid-β and tau) regulated by the glymphatic system. Latest studies have found that AD patients exhibit impairments to their glymphatic system. However, the alterations in the AD disease continuum, especially in the early stages, remain unclear. Moreover, the relationship between the glymphatic system and cognitive dysfunction is still worth exploring.
A novel diffusion tensor image analysis method was applied to evaluate the activity of the glymphatic system by an index for diffusivity along the perivascular space (ALPS-index). Based on this method, the activity of the glymphatic system was noninvasively evaluated in 300 subjects, including 111 normal controls (NC), 120 subjects with mild cognitive impairment (MCI), and 69 subjects with AD. Partial correlation analysis was applied to explore the association between glymphatic system and cognitive impairment based on three domain-general scales and several domain-specific cognitive scales. Receiver operating characteristic curve analysis was used to evaluate the classification performance of ALPS-index along the AD continuum.
ALPS-index was significantly different among NC, MCI and AD groups, and ALPS-index decreased with cognitive decline. In addition, ALPS-index was significantly correlated with the scores of the clinical scales (<0.05, FDR corrected), especially in left hemisphere. Furthermore, combination of ALPS and fractional anisotropy (FA) values achieved better classification results (NC vs. MCI: AUC = 0.6610, NC vs. AD: AUC = 0.8214).
Here, we show that the glymphatic system is closely associated with multiple cognitive dysfunctions, and ALPS-index can be used as a biomarker for alterations along the AD continuum. This may provide new targets and strategies for the treatment of AD, and has the potential to assist clinical diagnosis.
阿尔茨海默病（AD）是世界上著名的神经退行性疾病之一，它与由脑淋巴系统调节的两种蛋白质（淀粉样β蛋白和tau蛋白）的产生和清除平衡机制有关。最新研究发现，AD患者的脑淋巴系统存在功能障碍。然而，AD疾病连续体中的变化，尤其是在早期阶段，仍不清楚。此外，脑淋巴系统与认知功能障碍之间的关系仍值得探索。
应用一种新的扩散张量图像分析方法，通过沿血管周围间隙的扩散率指数（ALPS指数）来评估脑淋巴系统的活性。基于该方法，对300名受试者进行了脑淋巴系统活性的无创评估，包括111名正常对照（NC）、120名轻度认知障碍（MCI）受试者和69名AD受试者。应用偏相关分析，基于三个一般领域量表和几个特定领域认知量表探讨脑淋巴系统与认知障碍之间的关联。采用受试者工作特征曲线分析来评估ALPS指数在AD连续体中的分类性能。
NC、MCI和AD组之间的ALPS指数存在显著差异，且ALPS指数随认知功能下降而降低。此外，ALPS指数与临床量表得分显著相关（<0.05，经FDR校正），尤其是在左半球。此外，ALPS与分数各向异性（FA）值的组合取得了更好的分类结果（NC与MCI：AUC = 0.6610，NC与AD：AUC = 0.8214）。
在此，我们表明脑淋巴系统与多种认知功能障碍密切相关，ALPS指数可作为AD连续体中变化的生物标志物。这可能为AD的治疗提供新的靶点和策略，并有可能辅助临床诊断。
