Plasma neurofilament light chain (NfL) demonstrated to be a more valuable biomarker for neurodegeneration than total tau (T-tau) protein. This was the conclusion of the Mayo Clinic Study of Aging (MCSA), comparing the 2 biomarkers cross-sectionally and longitudinally [1]. These results suggest plasma NfL can be implemented into clinical practice.


T-tau and NfL both have demonstrated to be possible biomarkers of neurodegeneration in blood and cerebrospinal fluid, but a direct comparison between the 2 biomarkers in blood had not yet been performed. This study, presented by Dr Jordan Marks (Mayo Clinic, Minnesota, USA), included 995 participants without dementia. Data on plasma NfL and plasma T-tau, cognitive status, and neuroimaging were available. Possible associations between baseline NfL and T-tau levels and cognitive or neuroimaging outcomes were investigated through linear mixed effects models. Follow up was performed every 15 months (median 6.2 years). The results were validated in an Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (n=387) with a median follow up of 3.0 years. Elevated baseline NfL levels were more strongly associated with cognitive and neuroimaging outcomes than T-tau in all analyses: cross-sectional and longitudinal, global- and domain-specific, both for cognitive degeneration and neuroimaging outcomes. Importantly, the cross-sectional differences between the 2 biomarkers were small, whereas the longitudinal differences were more pronounced. Over time, baseline NfL levels were strongly associated with cognitive decline, decreasing cortical thickness and hippocampal volume, and an increased number of infarcts. The combination of both high NfL and T-tau levels was associated with lower memory and global cognitive z-scores, a decreased temporal lobe thickness, and an increased number of infarcts. According to Dr Marks, the findings in the ADNI cohort were consistent with the results of the MCSA. Dr Marks concluded by suggesting that plasma NfL levels might have a prognostic value for neurodegeneration and the combined NfL and T-tau levels could have diagnostic value. Consistency of the findings in the community-based (MSCA) and clinical (ADNI) cohorts shows that these results are applicable in clinical practice.

  1. Marks J, et al. Comparison of Neurofilament Light and Total Tau as Blood-Based Biomarkers of Neurodegeneration: Associations with Cognition and Neuroimaging Outcomes. ES.001, AAN 2021 Virtual Congress, 17-22 April.