Department of Psychology, Wayne State University, Detroit, MI 48202, USA.
Institute of Gerontology, Wayne State University, Detroit, MI 48202, USA.
Brain. 2024 Jan 4;147(1):12-25. doi: 10.1093/brain/awad267.
Over the past several years, there has been a surge in blood biomarker studies examining the value of plasma or serum neurofilament light (NfL) as a biomarker of neurodegeneration for Alzheimer's disease. However, there have been limited efforts to combine existing findings to assess the utility of blood NfL as a biomarker of neurodegeneration for Alzheimer's disease. In addition, we still need better insight into the specific aspects of neurodegeneration that are reflected by the elevated plasma or serum concentration of NfL. In this review, we survey the literature on the cross-sectional and longitudinal relationships between blood-based NfL levels and other, neuroimaging-based, indices of neurodegeneration in individuals on the Alzheimer's continuum. Then, based on the biomarker classification established by the FDA-NIH Biomarker Working group, we determine the utility of blood-based NfL as a marker for monitoring the disease status (i.e. monitoring biomarker) and predicting the severity of neurodegeneration in older adults with and without cognitive decline (i.e. a prognostic or a risk/susceptibility biomarker). The current findings suggest that blood NfL exhibits great promise as a monitoring biomarker because an increased NfL level in plasma or serum appears to reflect the current severity of atrophy, hypometabolism and the decline of white matter integrity, particularly in the brain regions typically affected by Alzheimer's disease. Longitudinal evidence indicates that blood NfL can be useful not only as a prognostic biomarker for predicting the progression of neurodegeneration in patients with Alzheimer's disease but also as a susceptibility/risk biomarker predicting the likelihood of abnormal alterations in brain structure and function in cognitively unimpaired individuals with a higher risk of developing Alzheimer's disease (e.g. those with a higher amyloid-β). There are still limitations to current research, as discussed in this review. Nevertheless, the extant literature strongly suggests that blood NfL can serve as a valuable prognostic and susceptibility biomarker for Alzheimer's disease-related neurodegeneration in clinical settings, as well as in research settings.
在过去的几年中，血液生物标志物研究如雨后春笋般涌现，研究人员探讨了血浆或血清神经丝轻链（NfL）作为阿尔茨海默病神经退行性变的生物标志物的价值。然而，人们很少努力结合现有研究结果来评估血液 NfL 作为阿尔茨海默病神经退行性变的生物标志物的效用。此外，我们仍需要更好地了解由血浆或血清 NfL 浓度升高反映的神经退行性变的具体方面。在这篇综述中，我们调查了文献中关于血液 NfL 水平与阿尔茨海默病连续体个体的神经影像学为基础的其他神经退行性变指标的横断面和纵向关系。然后，根据 FDA-NIH 生物标志物工作组建立的生物标志物分类，我们确定了血液 NfL 作为监测疾病状态（即监测生物标志物）和预测有或无认知能力下降的老年人神经退行性变严重程度的标志物的效用（即预后或风险/易感性生物标志物）。目前的研究结果表明，血液 NfL 作为监测生物标志物具有很大的潜力，因为血浆或血清中 NfL 水平的增加似乎反映了当前萎缩、低代谢和白质完整性下降的严重程度，尤其是在阿尔茨海默病通常受影响的大脑区域。纵向证据表明，血液 NfL 不仅可以作为预测阿尔茨海默病患者神经退行性变进展的预后生物标志物，而且可以作为易感性/风险生物标志物，预测认知正常但有更高患阿尔茨海默病风险的个体中脑结构和功能异常改变的可能性（例如，β-淀粉样蛋白水平较高的个体）。正如本综述中所讨论的，目前的研究仍存在局限性。尽管如此，现有文献强烈表明，血液 NfL 可作为临床和研究环境中阿尔茨海默病相关神经退行性变的有价值的预后和易感性生物标志物。
