Investigation on the Role of BDNF in the Benefits of Blueberry Extracts for the Improvement of Learning and Memory in Alzheimer's Disease Mouse Model

J Alzheimers Dis. 2017;56(2):629-640. doi: 10.3233/JAD-151108.


Background: Blueberry (BB) can provide a wide range of antioxidant benefits for AD. There is evidence that BB extracts could improve brain functions. However, the details are still unknown.

Objective: In the present study, we aimed to investigate the possible mechanism involved in the improvement of learning and memory capacity from BB extracts in AD.

Methods: APP/PS1 transgenic mice were fed BB extracts for 16 weeks. The capacity of learning and memory was assessed by Morris water maze (MWM) test, and long-term potentiation (LTP) was determined to evaluate hippocampal neuronal plasticity at the end of administration. Pathological changes in the brain were observed, and the expressions of brain-derived neurotrophic factor (BDNF) and extracellular signal-related kinase (ERK1/2) were determined to explore the mechanism of BB extract-induced benefits.

Results: AD mice exhibited more difficulties to learn and remember the exact position of the platform in the MWM test. The data showed that AD mice lacked effective learning in the platform search. In contrast, AD mice exhibited better performance both in the training phase and probe test of MWM after the BB treatment. Moreover, LTP was enhanced and the neuron loss was alleviated with BB treatment, while we did not find any obvious effect on the elimination of amyloid-β. In the AD mice, the expression of ERK1/2 was significantly increased (p < 0.05), while the level of BDNF was decreased (p < 0.05).

Conclusions: BB treatment was beneficial for the improvement of learning and memory of AD, and these effects might be related to the regulation of BDNF.

Keywords: APP/PS1; Alzheimer’s disease; blueberry; brain-derived neurotrophic factor; transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Blueberry Plants*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Disease Models, Animal
  • Female
  • Humans
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Maze Learning / drug effects
  • Mice, Transgenic
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Nootropic Agents / pharmacology*
  • Plant Extracts / pharmacology*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Spatial Memory / drug effects


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Brain-Derived Neurotrophic Factor
  • Nootropic Agents
  • PSEN1 protein, human
  • Plant Extracts
  • Presenilin-1