The polygenic hazard score mediates the association between plasma neurofilament light chain and brain morphometry in dementia spectrum.

Hamide Nasiri, Mohammad Hossein Azaraein, Shayan Shakeri, Mohammad Sadeghi, Ahmadreza Sohrabi-Ashlaghi, Soorin Berenjian, Shirin Karimian, Zahra Hoseinzadeh, Masoumeh Saberi Rounkian, Mahsa Mayeli
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Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

多基因危险评分介导痴呆谱中血浆神经丝轻链与脑形态测定的关联。
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)的重要生物标志物。此外,神经成像技术,如基于张量形态学(TBM),可以识别大脑的结构变化,可以为阿尔茨海默病的病理生理学提供有价值的见解。然而,遗传学在将基于血液的生物标志物和影像学结果联系起来方面的作用尚未得到很好的理解。因此,我们的目的是研究多基因危险评分(PHS)是否影响神经原纤维缠结和神经炎斑块以及脑影像学表现之间的关联。方法:使用阿尔茨海默病神经影像学倡议(ADNI)数据库,我们招募了所有可获得完整pNfL, PHS和TBM数据集的参与者。使用Python,我们分析了567名参与者的pNfL水平与TBM数据之间的关系,其中包括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如何与TBM措施相关方面的影响。结果:我们发现在MCI组和AD组中,加速TBM测量与NfL水平呈负相关。pNfL浓度预测MCI患者统计学和解剖学上加速的TMB测量。此外,PHS介导了AD患者统计TBM测量和NfL水平之间的关联,在考虑PHS后,NfL和TBM测量之间的显著关联消失。结论:我们发现尽管pNfL可以预测AD患者的认知能力下降和影像学表现,但这种作用是由PHS介导的。因此,在研究AD生物标志物及其相应的影像学表现时,应考虑小PHS。
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