👤 Tomasz Chmiela

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. Show less

Colony stimulating factor 1 receptor-related disorder (CSF1R-RD) is a rare, rapidly progressive neurodegenerative disease with significant clinical heterogeneity. Apolipoprotein E (ApoE) polymorphism, known to modulate microglial function and influence neurodegeneration, may act as a genetic modifier in CSF1R-RD. The objectives were to evaluate the distribution of ApoE alleles in CSF1R-RD and assess their association with clinical and neuropathological features. ApoE genotyping was performed in 55 individuals with CSF1R-RD. Clinical data from 25 deceased patients were analyzed based on ApoE genotype. Neuropathological evaluation was conducted on brain tissue from 14 patients, with semiquantitative scoring of white matter pathology and microglial burden. Statistical comparisons were made between carriers and noncarriers of the ApoE4 allele. ApoE allele frequencies in CSF1R-RD mirrored those of the general population (ε2: 7.3%, ε3: 79.1%, ε4: 13.6%). However, ApoE4 carriers exhibited significantly earlier symptom onset (median: 37.9 vs. 50.3 years, p = 0.0123) and death (median: 41.1 vs. 55.2 years, p = 0.0072). Neuropathological analysis revealed more severe white matter involvement and reduced microglial preservation in ApoE4 carriers (p = 0.034). Although ApoE allele distribution does not differ from the general population, the presence of the ApoE4 allele may influence the clinical trajectory and white matter pathology in CSF1R-RD. These findings suggest that ApoE polymorphism is a potential modifier of disease course and should be considered in therapeutic planning and future research. © 2026 International Parkinson and Movement Disorder Society. Show less