van der Kolk Nicolien M, Speelman Arlene D, van Nimwegen Marlies, Kessels Roy P C, IntHout Joanna, Hakobjan Marina, Munneke Marten, Bloem Bastiaan R, van de Warrenburg Bart P
Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Medical Psychology, Radboud University Medical Center, Nijmegen, the Netherlands.
Neurobiol Aging. 2015 Mar;36(3):1605.e1-6. doi: 10.1016/j.neurobiolaging.2014.08.023. Epub 2014 Aug 27.
Parkinson's disease (PD) is a neurodegenerative disorder caused by nigrostriatal dopaminergic degeneration. Brain-derived neurotrophic factor (BDNF) is a key protein in brain plasticity and is particularly important for survival of dopaminergic neurons. The Val66Met polymorphism of BDNF (rs6265) has been associated with functional differences (mainly cognitive) between healthy adults and also with differences in the clinical expression of several other neuropsychiatric illnesses including PD. However, these studies used different outcome measures, have not been replicated, and were cross sectional, making it difficult to establish the role of BDNF in the clinical variability of PD. Here, a large cohort of 384 PD patients were followed up for 2 years, and associations between BDNF genotype and various clinical characteristics were examined. The BDNF Met-allele carriers showed a significantly smaller decline in set shifting during follow-up compared with the homozygous BDNF Val-allele carriers. Contrary to previous assumptions, these results indicate that mental flexibility is one of the cognitive processes that may benefit from the BDNF Met allele in PD patients.
帕金森病（PD）是一种由黑质纹状体多巴胺能神经元变性引起的神经退行性疾病。脑源性神经营养因子（BDNF）是大脑可塑性中的一种关键蛋白质，对多巴胺能神经元的存活尤为重要。BDNF的Val66Met多态性（rs6265）与健康成年人之间的功能差异（主要是认知方面）以及包括PD在内的其他几种神经精神疾病的临床表型差异有关。然而，这些研究使用了不同的结局指标，尚未得到重复验证，且均为横断面研究，因此难以确定BDNF在PD临床变异性中的作用。在此，对384例PD患者的大型队列进行了为期2年的随访，并研究了BDNF基因型与各种临床特征之间的关联。与纯合BDNF Val等位基因携带者相比，BDNF Met等位基因携带者在随访期间的定势转换能力下降明显较小。与先前的假设相反，这些结果表明，心理灵活性是PD患者中可能从BDNF Met等位基因中获益的认知过程之一。
