Reduced blood-brain barrier expression of fatty acid-binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega-3 fatty acid diets

J Neurochem. 2018 Jan;144(1):81-92. doi: 10.1111/jnc.14249.


Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14 C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.

Keywords: Alzheimer's disease; blood-brain barrier; cognitive function; docosahexaenoic acid; fatty acid-binding protein; omega-3 fatty acids.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Blood-Brain Barrier*
  • Brain Chemistry
  • Cognition Disorders / etiology*
  • Cognition Disorders / genetics
  • Cognition Disorders / metabolism
  • Dietary Fats / administration & dosage
  • Docosahexaenoic Acids / deficiency
  • Docosahexaenoic Acids / pharmacokinetics*
  • Escherichia coli Proteins
  • Fatty Acid-Binding Proteins / biosynthesis
  • Fatty Acid-Binding Proteins / physiology*
  • Fatty Acids, Omega-3 / deficiency
  • Female
  • Humans
  • Male
  • Maze Learning
  • Memory Disorders / etiology
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation, Missense
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / physiology*
  • Polysaccharide-Lyases
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Recognition, Psychology
  • Recombinant Fusion Proteins / metabolism


  • Amyloid beta-Protein Precursor
  • Dietary Fats
  • Escherichia coli Proteins
  • Fabp5 protein, mouse
  • Fatty Acid-Binding Proteins
  • Fatty Acids, Omega-3
  • Neoplasm Proteins
  • PSEN1 protein, human
  • Presenilin-1
  • Recombinant Fusion Proteins
  • Docosahexaenoic Acids
  • KflA protein, E coli
  • Polysaccharide-Lyases