Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study

PLoS One. 2014 Jan 27;9(1):e86498. doi: 10.1371/journal.pone.0086498. eCollection 2014.


Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ.

Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.

Results: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401).

Conclusions: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / metabolism
  • Atrophy
  • Australia
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology*
  • Cross-Sectional Studies
  • Female
  • Genetic Association Studies
  • Genotype
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory Disorders / genetics*
  • Mutation, Missense / genetics
  • Positron-Emission Tomography


  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human

Grant support

Funding for the study was provided in part by the study partners [Australian Commonwealth Scientific Industrial and research Organization, Edith Cowan University, Mental Health Research institute, Alzheimer’s Australia), National Ageing Research Institute, Austin Health, CogState Ltd., Hollywood Private Hospital, Sir Charles Gardner Hospital]. The study also received support from the National Health and Medical Research Council and the Dementia Collaborative Research Centres program, as well as ongoing funding from the Science and Industry Endowment Fund. The authors also acknowledge the financial support of the Cooperative Research Centre for Mental Health, from the Australian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. PM is a full-time employee of CogState Ltd. SML is supported by the Cooperative Research Centre for Mental Health, which is an Australian Response to Reviewers government initiative. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.