Objective  To systematic evaluate the change of serum neurofilament light chain protein (NfL) level in patients with different neurodegenerative disease and different degrees of cognitive impairment.

Methods  A comprehensive search of literatures was conducted in the PubMed, Embase, Web of Science, CNKI, Wanfang and CBM from inception to April 30, 2023. Literatures with serum NfL levels in patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and healthy controls were included in the cohort or case-control studies. The Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. RevMan 5.4 software was used to analyze the change of serum NfL between exposure group and non-exposure group. The effect size was expressed by standard mean difference (SMD) and 95% confidence interval (CI).

Results  62 comparative studies extracted from a total of 43 literatures were included. Comparing PD, AD, MSA, PSP with their respective healthy control groups, the four groups included 9, 24, 9, and 8 studies, respectively. The levels of serum NfL in the PD group [SMD=0.27, 95%CI (0.17, 0.36)], AD group [SMD=0.97, 95%CI (0.70, 1.23)], MSA group [SMD=1.51, 95%CI (0.97, 2.05)], and PSP group [SMD=1.54 95%CI (1.14, 1.93)] were higher than those in the healthy controls in their respective groups. Further comparison was conducted between PD normal cognitive (PD-NC) and PD with dementia (PD-D), AD mild cognitive impairment (AD-MCI) and AD with dementia (AD-D) groups. 3 and 9 studies were included in the two comparison groups, respectively. The serum NfL levels of PD-D patients were higher than those of PD-NC patients [SMD=0.92, 95%CI (0.63, 1.20)], and the serum NfL levels of AD-D patients were higher than those of AD-MCI patients [SMD=0.61, 95%CI (0.49, 0.72)].

Conclusion  The serum NfL levels in patients with PD, AD, MSA, and PSP are higher than those in healthy individuals, and the greater the degree of cognitive impairment, the higher the serum NfL levels. Serum NfL may be a potential peripheral biomarker reflecting neurodegenerative diseases, which can further reflect the decline in cognitive levels.

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