Nasiri Hamide, Azaraein Mohammad Hossein, Shakeri Shayan, Sadeghi Mohammad, Sohrabi-Ashlaghi Ahmadreza, Berenjian Soorin, Karimian Shirin, Hoseinzadeh Zahra, Rounkian Masoumeh Saberi, Mayeli Mahsa
Student Research Committee, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran.
Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Iranian Scientific Society of Clinical Hypnosis, Tehran, Iran.
Arch Gerontol Geriatr. 2025 Mar;130:105703. doi: 10.1016/j.archger.2024.105703. Epub 2024 Nov 25.
Blood-based biomarkers such as plasma neurofilament light chain (pNfL) are crucial biomarkers for Alzheimer's disease (AD). Additionally, neuroimaging techniques such as tensor-based morphometry (TBM), which identify structural changes in the brain, can provide valuable insights into AD pathophysiology. However, the role of genetics in linking the blood based biomarkers and imaging findings has not been well understood. Therefore, we aimed to investigate whether the polygenic hazard score (PHS), affects the association between neurofibrillary tangles and neuritis plaques and brain imaging findings.
Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we enrolled all participants for whom a complete dataset of pNfL, PHS, and TBM was available. Using Python, we analyzed the associations between pNfL levels and the TBM data of 567 participants incluidng 152 cognitively normal individuals, 309 participants with mild cognitive impairment (MCI), and 106 patients with AD. We used a mediation analysis to identify the effect of PHS in how pNfL is associated with TBM measures.
We found a negative correlation between the accelerated TBM measure and NfL levels in both the MCI and AD groups. The pNfL concentration predicted both accelerated statistical and anatomical TMB measures in patients with MCI. Furthermore, PHS mediatedthe association between statistical TBM measures and NfL levels in AD patients, to the extent that the significant association between NfL and TBM measures disappeared after accounting for PHS.
We showed that although pNfL can predict the cognitiee decline and imaging findings in AD, this effect is mediated by the PHS. Therefore, PHS should be considered when investigating AD biomarkers and their corresponding imaging findings.
基于血液的生物标志物，如血浆神经丝轻链（pNfL），是阿尔茨海默病（AD）的关键生物标志物。此外，诸如基于张量的形态测量（TBM）等神经成像技术，可识别大脑结构变化，能为AD病理生理学提供有价值的见解。然而，遗传学在连接基于血液的生物标志物和成像结果方面的作用尚未得到充分理解。因此，我们旨在研究多基因风险评分（PHS）是否会影响神经原纤维缠结和神经炎斑块与脑成像结果之间的关联。
利用阿尔茨海默病神经成像倡议（ADNI）数据库，我们纳入了所有可获得pNfL、PHS和TBM完整数据集的参与者。我们使用Python分析了567名参与者的pNfL水平与TBM数据之间的关联，这些参与者包括152名认知正常个体、309名轻度认知障碍（MCI）参与者和106名AD患者。我们使用中介分析来确定PHS在pNfL与TBM测量值关联方式中的作用。
我们发现，在MCI组和AD组中，加速TBM测量值与NfL水平之间均呈负相关。pNfL浓度可预测MCI患者的加速统计和解剖学TMB测量值。此外，PHS介导了AD患者中统计TBM测量值与NfL水平之间的关联，以至于在考虑PHS后，NfL与TBM测量值之间的显著关联消失。
我们表明，尽管pNfL可预测AD中的认知衰退和成像结果，但这种效应由PHS介导。因此，在研究AD生物标志物及其相应的成像结果时应考虑PHS。
