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Neural Plasticity
Volume 2016, Article ID 6846721, 15 pages
Research Article

A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

1Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands
2Department of Geriatric Medicine, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands
3Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands
4Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany
5Nutricia Research, Advanced Medical Nutrition, Utrecht, Netherlands
6UIPS, Utrecht University, Utrecht, Netherlands

Received 8 January 2016; Accepted 22 February 2016

Academic Editor: Tae-Jin Kim

Copyright © 2016 Maximilian Wiesmann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer’s disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging.