Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

P.-H. Lin, S.-J. Tsai, C.-W. Huang, L. Mu-En, S.-W. Hsu, C.-C. Lee, N.-C. Chen, Y.-T. Chang, M.-Y. Lan, Chia-Chen Chang

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

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 memoryrelated 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). Seedbased 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.
Original languageAmerican English
Pages (from-to)54200-54214
JournalOncotarget
Volume7
Issue number34
DOIs
StatePublished - 2016

Keywords

  • Anatomical structural covariance
  • Anatomical structural covariance
  • Brain-derived neurotrophic factor
  • Brain-derived neurotrophic factor
  • Default mode network
  • Default mode network
  • Genetic dosage effect
  • Genetic dosage effect
  • Gerotarget
  • Gerotarget

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