Brain Structure and Function

, Volume 219, Issue 5, pp 1841–1868 | Cite as

Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice

  • Diane Jansen
  • Valerio Zerbi
  • Carola I. F. Janssen
  • Daan van Rooij
  • Bastian Zinnhardt
  • Pieter J. Dederen
  • Alan J. Wright
  • Laus M. Broersen
  • Dieter Lütjohann
  • Arend Heerschap
  • Amanda J. KiliaanEmail author
Original Article


Lipid metabolism and genetic background together strongly influence the development of both cardiovascular and neurodegenerative diseases like Alzheimer’s disease (AD). A non-pharmacological way to prevent the genotype-induced occurrence of these pathologies is given by dietary behavior. In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in two models for atherosclerosis and vascular risk factors in AD: the apolipoprotein ε4 (apoE4) and the apoE knockout (apoE ko) mice. This specific multi-nutrient diet was developed to support neuronal membrane synthesis and was expected to contribute to the maintenance of vascular health. At 12 months of age, both genotypes showed behavioral changes compared to control mice and we found increased neurogenesis in apoE ko mice. The specific multi-nutrient diet decreased anxiety-related behavior in the open field, influenced sterol composition in serum and brain tissue, and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that wild-type and apoE ko mice fed with this multi-nutrient diet showed locally increased cerebral blood volume and decreased hippocampal glutamate levels. Taken together, these data suggest that a specific dietary intervention has beneficial effects on early pathological consequences of hypercholesterolemia and vascular risk factors for AD.


Alzheimer’s disease Amyloid Apolipoprotein E Blood volume Cerebrovascular circulation Cholesterol Doublecortin Exploratory behavior Fatty acids Magnetic resonance spectroscopy Maze learning Memory Nutrition Synaptophysin Transgenic mice 



We would like to thank Nick van Wijk and Martin Balvers for supplying the diets and for the analysis of the brain fatty acids. The authors would also like to acknowledge Ilse Arnoldussen, Xiaotian Fang, Maartje Mutsaers, Anne Rijpma and Maximilian Wiesmann for their laboratory work. Furthermore, we would like to thank Andor Veltien and Sjaak van Asten for their technical support with the MR experiments. The authors would also like to acknowledge Janneke Mulders and Denise Tax for their excellent care giving of our mice. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no211696 (LipidiDiet) and was supported by NWO investment grants nr 91106021 and BIG (VISTA).

Conflict of interest

LMB is an employee of Nutricia Advanced Medical Nutrition, Danone Research. There are no actual or potential conflicts of interest to report for any of the other authors.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Diane Jansen
    • 1
  • Valerio Zerbi
    • 1
  • Carola I. F. Janssen
    • 1
  • Daan van Rooij
    • 1
  • Bastian Zinnhardt
    • 1
  • Pieter J. Dederen
    • 1
  • Alan J. Wright
    • 2
  • Laus M. Broersen
    • 3
  • Dieter Lütjohann
    • 4
  • Arend Heerschap
    • 2
  • Amanda J. Kiliaan
    • 1
    Email author
  1. 1.Department of AnatomyRadboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and BehaviourNijmegenThe Netherlands
  2. 2.Department of RadiologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised NutritionWageningenThe Netherlands
  4. 4.Institute for Clinical Chemistry and Clinical PharmacologyUniversity Clinics BonnBonnGermany

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