title: Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease.
abstract: Nutritional intervention may retard the development of Alzheimer's disease (AD). In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model (APPswe/PS1dE9). One diet contained membrane precursors such as omega-3 fatty acids and uridine monophosphate (DEU), whereas another diet contained cofactors for membrane synthesis as well (Fortasyn); the diets were developed to enhance synaptic membranes synthesis, and contain components that may improve vascular health. We measured cerebral blood flow (CBF) and water diffusivity with ultra-high-field magnetic resonance imaging, as alterations in these parameters correlate with clinical symptoms of the disease. APPswe/PS1dE9 mice on control diet showed decreased CBF and changes in brain water diffusion, in accordance with findings of hypoperfusion, axonal disconnection and neuronal loss in patients with AD. Both multinutrient diets were able to increase cortical CBF in APPswe/PS1dE9 mice and Fortasyn reduced water diffusivity, particularly in the dentate gyrus and in cortical regions. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms.
authors.affiliation: Department of Anatomy, Donders Institute for Brain Cognition & Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.forename: Diane
authors.initials: D
authors.lastname: Jansen
authors.forename: Maximilian
authors.initials: M
authors.lastname: Wiesmann
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Fang
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
authors.forename: Andor
authors.initials: A
authors.lastname: Veltien
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy* / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents; D053764:Presenilin-1 / Q000235:genetics; D014542:Uridine Monophosphate / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; D053764:Presenilin-1; C580804:presenilin 1, mouse; D014542:Uridine Monophosphate
keywords: AD mouse model; APPswe/Ps1de9; Alzheimer's disease; Cerebral blood flow; Diffusion tensor imaging; MRI; Mice; Nutrition; Omega-3 fatty acids