title: Combination of apolipoprotein E4 and high carbohydrate diet reduces hippocampal BDNF and arc levels and impairs memory in young mice.
abstract: The presence of the E4 allele of apolipoprotein E (apoE) is the strongest known genetic risk factor for sporadic Alzheimer's disease (AD). Other risk factors for developing AD have been identified, including lifestyle such as dietary habits. The present study was designed to explore the impact of the interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning and memory retention. As an investigative model, we compared young apoE3 and apoE4 target replacement mice fed on a HCD for 6 months. Our results indicate that HCD compromises memory processes in apoE4 mice. ApoE4 mice on HCD showed decreased activity-regulated cytoskeletal-associated protein (Arc) and brain derived neurotrophic factor (BDNF) levels, as well as decreased BDNF signaling in the hippocampus. In contrast, apoE3 mice were resistant to the deleterious effects of HCD on both behavior and memory-related proteins. Our results support the hypothesis that already in mid-life, genetic, and environmental risk factors act together on the mechanisms behind cognitive impairment.
authors: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Alzheimer Disease Research Center, NOVUM, Stockholm, Sweden. Silvia.Maioli@ki.se
authors: Silvia
authors: S
authors: Maioli
authors: Elena
authors: E
authors: Puerta
authors: Paula
authors: P
authors: Merino-Serrais
authors: Laura
authors: L
authors: Fusari
authors: Francisco
authors: F
authors: Gil-Bea
authors: Roberto
authors: R
authors: Rimondini
authors: Angel
authors: A
authors: Cedazo-Minguez
mesh_terms: D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D053327:Apolipoprotein E4; D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D004040:Dietary Carbohydrates; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein