Serum neurofilament light chain level as a predictor of cognitive stage transition

Eun Hye Lee, Hyuk Sung Kwon, Seong Ho Koh, Seong Hye Choi, Jeong Hwa Jin, Jee Hyang Jeong, Jae Won Jang, Kyung Won Park, Eun Joo Kim, Hee Jin Kim, Jin Yong Hong, Soo Jin Yoon, Bora Yoon, Ju Hee Kang, Jong Min Lee, Hyun Hee Park, Jungsoon Ha

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18 Scopus citations


Background: Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. Methods: This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high. Results: The Kaplan–Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor. Conclusion: The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.

Original languageEnglish
Article number6
JournalAlzheimer's Research and Therapy
Issue number1
StatePublished - Dec 2022

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  • Alzheimer’s disease
  • Amyloid pathology
  • Cognitive stage
  • Cortical thickness
  • Neurofilament light chain


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