# BDNF and GDNF in Parkinson’s Disease: Associations with Clinical Features, Disease Course, and Progression—A Systematic Review

## TL;DR

This review explores how BDNF and GDNF levels relate to Parkinson’s disease symptoms, progression, and treatment effects.

## Contribution

The study systematically reviews the associations between BDNF/GDNF levels and clinical features of Parkinson’s disease.

## Key findings

- Lower BDNF levels are linked to severe motor symptoms and cognitive decline in Parkinson’s disease.
- Levodopa treatment may increase BDNF levels in advanced Parkinson’s disease.
- Reduced GDNF and BDNF levels are associated with depression and cognitive decline in Parkinson’s patients.

## Abstract

Glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are proteins essential for neuronal survival and implicated in Parkinson’s disease (PD) pathophysiology. Although reduced levels of these neurotrophins have been observed in PD, their relationship with disease progression remains unclear. We conducted a systematic review by independently searching four databases using predefined keywords: Parkinson AND (GDNF OR BDNF OR neurotroph) AND (serum OR blood OR cerebrospinal fluid). After screening 2132 records, 35 studies qualified for inclusion. Changes in neurotrophic factors’ levels were evaluated in relation to disease severity and duration. Many studies reported a decline in BDNF levels associated with more severe motor symptoms. Some studies noted increased BDNF levels in advanced PD. This pattern may be affected by levodopa treatment, suggesting that elevated BDNF levels in advanced PD could reflect a treatment-related effect rather than disease progression itself. Reduced levels of both GDNF and BDNF were linked to cognitive decline, with BDNF also decreased in PD patients with depression. Serum BDNF levels were associated with motor severity and neuropsychiatric symptoms. BDNF levels in PD may increase with longer disease duration, likely due to levodopa treatment effects. However, lower BDNF levels are seen in cognitive decline and depression, frequent non-motor symptoms of PD. Further research is required to clarify BDNF dynamics and to determine GDNF’s role in motor progression and cognitive decline.

The online version contains supplementary material available at 10.1007/s12035-025-05649-z.