Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: A systematic review and meta-analysis

Background: Brain-derived neurotrophic factor (BDNF) is an abundant neurotrophin in the adult brain. Serum BDNF levels might be used as a proxy for its central expression. Considering conflicting reports, we aimed to answer How do serum/CSF levels of BDNF change in patients with PD?. Methods: We conducted a comprehensive search in MEDLINE, EMBASE and SCOPUS databases including 12 eligible studies. Five studies compared BDNF in serum of PD patients versus healthy controls (HC) and 3 studies provided BDNF levels in sera of non-depressed and depressed PD patients (NDPD and DPD). Review Manager and Software version 3.0 were used for meta-analysis and meta-regressions. Mean difference (MD) was used for measurement of effect size. Results: PD patients had reduced serum BDNF levels compared to HC (MD = -2.99 ng/mL). Serum BDNF was highest in DPD patients compared to HC (MD = -4.83 ng/mL), with no difference between DPD and NDPD patients in serum BDNF levels. Among co-variates that were eligible for meta-regression, age, sex, and Hoehn and Yahr (H&Y) motor stage had significant positive associations with the effect size in the difference of serum BDNF between patients and HC. Conclusions: PD patients had reduced serum BDNF levels compared to HC, regardless of presence of co-morbid depression. PD is at least equally effective in reducing serum BDNF levels as depression. Motor progression predicts serum BDNF downregulation in PD. Acute exercise improves motor function and depressive symptoms in PD probably via BDNF upregulation. The paradoxical rise in serum BDNF in advance PD is probably compensatory in nature.