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Longitudinal Implications of the BDNF rs6265 Polymorphism for Motor and Nonmotor Features of Parkinson’s Disease in the Korean Population

Year: 2026

Type: article

Abstract: OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been suggested to support the endurance and dopamine release of dopaminergic neurons. Its Val66Met polymorphism might modify Parkinson's disease (PD) evolution, although evidence in Asian populations remains limited. This study aimed to explore how the BDNF rs6265 genotype is associated with the clinical characteristics and longitudinal progression patterns of PD patients in a Korean population. METHODS: A total of 247 patients were enrolled and followed for a mean duration of 50.9±23.9 months. Baseline and/or periodic assessments captured motor severity, nonmotor burden, cognition, orthostatic stress, cardiac denervation, and presynaptic dopamine transporter availability. The repeated measures were manipulated to infer any genotypic differences in the trajectories of each clinical domain. RESULTS: The genotype frequencies were 31.2% (77/247) for Val/Val carriers and 68.8% (170/247) for Met-allele carriers. Baseline clinical characteristics and presynaptic dopamine transporter availability were comparable between genotypes. Initially, Val homozygotes showed more preserved myocardial innervation and poorer nonfrontal cognitive performance. Longitudinal analyses demonstrated genotype-specific increases in motor and cognitive severity. Compared with Met-allele carriers, the homozygous Val group exhibited accelerated motor progression and a more rapid decline in the frontal domain after 3 years of follow-up. CONCLUSION: The differences in myocardial denervation at diagnosis, cognitive profiles, and motor progression might suggest a potential modulatory role of BDNF polymorphisms in PD progression in the Korean population.

Source: Journal of Movement Disorders

DOI: 10.14802/jmd.25300

Authors: Sang-Won Yoo, Yun Joong Kim, Dong-Woo Ryu, Yoonsang Oh, Seunggyun Ha, Joong-Seok Kim

Institutions: Catholic University of Korea, Yonsei University, Yonsei University Health System

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond