title: A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice.
abstract: 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.
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands; Department of Geriatric Medicine, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Wiesmann
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Jansen
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Haast
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.affiliation: Nutricia Research, Advanced Medical Nutrition, Utrecht, Netherlands; UIPS, Utrecht University, Utrecht, Netherlands.
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition & Behaviour, Radboud University Medical Center, 6525 EZ Nijmegen, Netherlands.
authors.forename: Amanda J
authors.identifier: 0000-0002-2158-6210
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000178:diet therapy* / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D001931:Brain Mapping; D004032:Diet; D000076122:Disks Large Homolog 4 Protein; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D051528:Guanylate Kinases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D013261:Sterols / Q000097:blood
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005227:Fatty Acids; D008565:Membrane Proteins; D013261:Sterols; D051528:Guanylate Kinases