Neurofilament Light Chain as a Potential Biomarker in Plasma for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and a Meta-Analysis

Background: Plasma neurofilament light (NfL) is an intermediate filamentous protein involved in stabilizing axonal structure and promoting axon growth. Recent clinical studies have reported increased NfL levels in the plasma of Alzheimer's disease (AD) patients and patients with mild cognitive impairment (MCI). This study used meta-analysis to evaluate the potential of plasma NfL as a biomarker for patients with AD and MCI. Methods: PubMed, Embase, and Web of Science databases were systematically searched for studies of plasma NfL levels in AD and MCI, and a meta-analysis was employed to identify whether it was suited as a reliable biomarker and discrimination of healthy controls. Results: A total of 24 published articles that included 2397 AD and 3242 MCI patients were analysed. The level of plasma NfL was significantly increased in patients with AD and MCI when compared with healthy control subjects (standard mean difference [SMD]: 14.33 [12.42-16.24], z = 14.71, p < 0.00001; SMD: 4.95 [3.82-6.80], z = 8.59, p < 0.00001) and higher in AD patients than MCI patients (SMD: 9.32 [8.07-10.57], z = 14.62, p < 0.00001). Meta-regression analysis showed a negative relationship between Mini-Mental State Examination (MMSE) scores and plasma NfL levels in MCI patients (slope = -0.399 [95% confidence interval (CI): -0.518 to -0.281], p < 0.05). Conclusions: The meta-analysis suggested that NfL levels increased in the plasma of patients with AD and MCI and were associated with cognitive decline. Results provide the clinical evidence to support plasma NfL as a cognitive biomarker for AD and MCI.