Department of Imaging, The Fifth People's Hospital of Shanghai, Fudan University, No.128 Ruili Road, Minhang District, Shanghai, 200240, China.
BMC Neurol. 2024 Jul 6;24(1):236. doi: 10.1186/s12883-024-03728-7.
Neurofilament Light (NfL) is a biomarker for early neurodegeneration in Alzheimer's disease (AD). This study aims to examine the association between plasma NfL and multi-modal neuroimaging features across the AD spectrum and whether NfL predicts future tau deposition.
The present study recruited 517 participants comprising Aβ negative cognitively normal (CN-) participants (n = 135), Aβ positive cognitively normal (CN +) participants (n = 64), individuals with amnestic mild cognitive impairment (aMCI) (n = 212), and those diagnosed with AD dementia (n = 106). All the participants underwent multi-modal neuroimaging examinations. Cross-sectional and longitudinal associations between plasma NfL and multi-modal neuro-imaging features were evaluated using partial correlation analysis and linear mixed effects models. We also used linear regression analysis to investigate the association of baseline plasma NfL with future PET tau load. Mediation analysis was used to explore whether the effect of NfL on cognition was mediated by these imaging biomarkers.
The results showed that baseline NfL levels and the rate of change were associated with Aβ deposition, brain atrophy, brain connectome, glucose metabolism, and brain perfusion in AD signature regions (P<0.05). In both Aβ positive CN and MCI participants, baseline NfL showed a significant predictive value of elevating tau burden in the left medial orbitofrontal cortex and para-hippocampus (β = 0.336, P = 0.032; β = 0.313, P = 0.047). Lastly, the multi-modal neuroimaging features mediated the association between plasma NfL and cognitive performance.
The study supports the association between plasma NfL and multi-modal neuroimaging features in AD-vulnerable regions and its predictive value for future tau deposition.
神经丝轻链（NfL）是阿尔茨海默病（AD）早期神经退行性变的生物标志物。本研究旨在探讨 AD 谱中血浆 NfL 与多模态神经影像学特征之间的关联，以及 NfL 是否可以预测未来的 tau 沉积。
本研究共招募了 517 名参与者，包括 Aβ阴性认知正常（CN-）参与者（n=135）、Aβ阳性认知正常（CN+）参与者（n=64）、遗忘型轻度认知障碍（aMCI）个体（n=212）和 AD 痴呆诊断患者（n=106）。所有参与者均接受了多模态神经影像学检查。采用偏相关分析和线性混合效应模型评估了血浆 NfL 与多模态神经影像学特征之间的横断面和纵向关联。我们还使用线性回归分析探讨了基线血浆 NfL 与未来 PET tau 负荷之间的关联。采用中介分析来探讨 NfL 对认知的影响是否通过这些影像学生物标志物介导。
结果显示，基线 NfL 水平和变化率与 AD 特征区域的 Aβ 沉积、脑萎缩、脑连接组、葡萄糖代谢和脑灌注相关（P<0.05）。在 Aβ 阳性 CN 和 MCI 参与者中，基线 NfL 对左侧内侧眶额皮质和海马旁回 tau 负荷升高具有显著的预测价值（β=0.336，P=0.032；β=0.313，P=0.047）。最后，多模态神经影像学特征介导了血浆 NfL 与认知表现之间的关联。
该研究支持了 AD 易感区域中血浆 NfL 与多模态神经影像学特征之间的关联及其对未来 tau 沉积的预测价值。
