Blood levels of brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis (MS): A systematic review and meta-analysis

Background: Multiple sclerosis is an autoimmune demyelinating disease marked by the involvement of multiple pathophysiological pathways, including BDNF. BDNF (brain-derived neurotrophic factor) is one of the main neurotrophic factors in the adult brain. The amount of BDNF in the blood can be utilized as a surrogate for the central expression of this marker. Given contradicting reports, we set out to answer the question, “How do blood levels of BDNF differ in people with multiple sclerosis (PwMS) compared to controls?” Methods: We performed a thorough search in MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases, resulting in 13 eligible investigations. Eleven studies compared BDNF in serum of PwMS versus healthy controls (HC), and two studies provided BDNF levels in the plasma of PwMs. R version 4.0.4 was used for meta-analysis and visualizations. Mean difference (MD) was used for the measurement of effect size. Results: The final analysis included thirteen studies with 689 patients with MS and 583 controls. The preliminary results indicated that MS patients had statistically significant lower levels of BDNF than controls: SMD -5.1992 (95% CI [-8.4488; -1.9496], p-value < 0.0001. Additionally, subgroup analysis revealed a statistically significant difference in serum and plasma levels (p-value=0.01). Performing univariate meta-regression, disease duration and the proportion of males had, respectively, a significant negative and positive correlation with BDNF levels. Conclusion: Circulating levels of BDNF are decreased in MS. Future studies should investigate the role of BDNF as a biomarker of disease severity and/or progression for a personalized approach to MS.