Saberian Parsa, Nasiri Hamide, Kaffashian Fatemeh, Nasiriansari Parisa, Nasab Fatemeh Nazari, Mehrvarz Niusha, Talebizadeh Fatemeh, Shakeri Shayan, Mayeli Mahsa
Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Student Research Committee,School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
IBRO Neurosci Rep. 2025 May 1;18:732-738. doi: 10.1016/j.ibneur.2025.04.018. eCollection 2025 Jun.
Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by progressive cognitive decline and disrupted brain network connectivity, particularly within the default mode network (DMN). Neurofilament light chain (NfL) serves as a biomarker for axonal injury, but the role of genetic predisposition, assessed via the Polygenic Hazard Score (PHS), in mediating the association between plasma NfL and DMN connectivity remains unclear. This study investigates whether PHS mediates the association between plasma NfL levels and DMN connectivity in individuals across different cognitive stages, including cognitively normal (CN), mild cognitive impairment (MCI), and AD.
Data were extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Plasma NfL concentrations were measured using the Simoa assay, and resting-state fMRI (rs-fMRI), assessed DMN connectivity. The cohort included 102 participants (nCN=28, nMCI=52, and nAD=22). Partial correlation analyses and mediation models were performed, adjusting for age and gender. Statistical significance was set at p < 0.05, after corrections for multiple comparisons.
Plasma NfL levels were significantly higher in AD group compared to CN and MCI groups (p = 0.030). DMN connectivity showed substantial declines in the AD group, particularly in the posterior and ventral regions. Significant negative correlations were observed between plasma NfL and ventral DMN connectivity in AD. However, mediation analysis indicated no significant indirect effect of PHS, suggesting that genetic risk does not mediate the plasma NfL-DMN association.
These findings suggest that elevated plasma NfL levels are associated with disrupted ventral DMN connectivity in AD, reflecting neurodegeneration-related network dysfunction. However, the lack of a mediating effect by PHS indicates that this relationship is likely independent of genetic risk burden.
not applicable.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，其特征为进行性认知衰退和大脑网络连接中断，尤其是在默认模式网络（DMN）内。神经丝轻链（NfL）作为轴突损伤的生物标志物，但通过多基因风险评分（PHS）评估的遗传易感性在介导血浆NfL与DMN连接性之间关联中的作用仍不清楚。本研究调查了PHS是否介导不同认知阶段个体（包括认知正常（CN）、轻度认知障碍（MCI）和AD）血浆NfL水平与DMN连接性之间的关联。
数据取自阿尔茨海默病神经影像倡议（ADNI）。使用单分子阵列（Simoa）分析法测量血浆NfL浓度，并通过静息态功能磁共振成像（rs-fMRI）评估DMN连接性。该队列包括102名参与者（nCN = 28，nMCI = 52，nAD = 22）。进行了偏相关分析和中介模型分析，并对年龄和性别进行了校正。在进行多重比较校正后，将统计学显著性设定为p < 0.05。
与CN组和MCI组相比，AD组的血浆NfL水平显著更高（p = 0.030）。AD组的DMN连接性显著下降，尤其是在后部和腹侧区域。在AD患者中，观察到血浆NfL与腹侧DMN连接性之间存在显著负相关。然而，中介分析表明PHS没有显著的间接效应，这表明遗传风险并未介导血浆NfL与DMN之间存在的关联。
这些发现表明，AD患者血浆NfL水平升高与腹侧DMN连接性中断有关，反映了与神经退行性变相关的网络功能障碍。然而，PHS缺乏中介作用表明这种关系可能独立于遗传风险负担。
不适用。
