title: Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease.
abstract: In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor.Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.
authors: Department of Health and Beauty, Shu-Zen College of Medicine and Management, Kaohsiung, Taiwan.
authors: Pin-Hsuan
authors: PH
authors: Lin
authors: Psychiatric Department of Taipei Veterans General Hospital, Taipei, Taiwan.|Psychiatric Division, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Shih-Jen
authors: SJ
authors: Tsai
authors: Department of Health and Beauty, Shu-Zen College of Medicine and Management, Kaohsiung, Taiwan.|Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chi-Wei
authors: CW
authors: Huang
authors: Psychiatric Division, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Liu
authors: L
authors: Mu-En
authors: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Shih-Wei
authors: SW
authors: Hsu
authors: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chen-Chang
authors: CC
authors: Lee
authors: Department of Health and Beauty, Shu-Zen College of Medicine and Management, Kaohsiung, Taiwan.|Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Nai-Ching
authors: NC
authors: Chen
authors: Department of Health and Beauty, Shu-Zen College of Medicine and Management, Kaohsiung, Taiwan.|Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Ya-Ting
authors: YT
authors: Chang
authors: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Min-Yu
authors: MY
authors: Lan
authors: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Chiung-Chih
authors: CC
authors: Chang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013702:Temporal Lobe / Q000000981:diagnostic imaging
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Alzheimer’s disease; Gerotarget; anatomical structural covariance; brain-derived neurotrophic factor; default mode network; genetic dosage effect