Brain Science Advances


Alzheimer’s disease, plasma neurofilament light (NFL), longitudinal, neurodegeneration


Objective:To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD).Methods:A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion.Results:Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally (p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time (p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model.Conclusion:Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.


Tsinghua University Press