title: Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.
abstract: Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD). We first observed that cerebral expression of human AD transgenes led to peripheral glucose intolerance, associated with pancreatic human Aβ accumulation. High-fat diet enhanced glucose intolerance, brain soluble Aβ, and memory impairment in 3xTg-AD mice. Strikingly, a single insulin injection reversed the deleterious effects of HFD on memory and soluble Aβ levels, partly through changes in Aβ production and/or clearance. Our results are consistent with the development of a vicious cycle between AD and diabetes, potentiating both peripheral metabolic disorders and AD neuropathology. The capacity of insulin to rapidly break the deleterious effects of this cycle on soluble Aβ concentrations and memory has important therapeutic implications.
authors.affiliation: Faculté de Pharmacie, Université Laval, Québec, Canada Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada Institut des Nutraceutiques et des Aliments Fonctionnels, Université Laval, Québec, Canada.
authors.forename: Milene
authors.initials: M
authors.lastname: Vandal
authors.affiliation: Institut des Nutraceutiques et des Aliments Fonctionnels, Université Laval, Québec, Canada Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute, Durham, NC Département de Medicine, Axe de Cardiologie, Faculté de Médicine de l'Université Laval, Québec, Canada Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: White
authors.affiliation: Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
authors.forename: Cyntia
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: Faculté de Pharmacie, Université Laval, Québec, Canada Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada Département de Recherche et Développement, Héma-Québec, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.affiliation: Institut des Nutraceutiques et des Aliments Fonctionnels, Université Laval, Québec, Canada Département de Medicine, Axe de Cardiologie, Faculté de Médicine de l'Université Laval, Québec, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chevrier
authors.affiliation: Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Emond
authors.affiliation: Faculté de Pharmacie, Université Laval, Québec, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lefrançois
authors.affiliation: Faculté de Pharmacie, Université Laval, Québec, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Virgili
authors.affiliation: Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Planel
authors.affiliation: Faculté de Médicine, Université Laval, Québec, Canada Centre de Recherche du Centre Hospitalier de l'Université de Québec, Hôpital Saint-François d'Assise, Québec, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Giguere
authors.affiliation: Institut des Nutraceutiques et des Aliments Fonctionnels, Université Laval, Québec, Canada Département de Medicine, Axe de Cardiologie, Faculté de Médicine de l'Université Laval, Québec, Canada Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
authors.forename: Andre
authors.initials: A
authors.lastname: Marette
authors.affiliation: Faculté de Pharmacie, Université Laval, Québec, Canada Axe Neurosciences, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada Institut des Nutraceutiques et des Aliments Fonctionnels, Université Laval, Québec, Canada frederic.calon@crchul.ulaval.ca.
authors.forename: Frederic
authors.initials: F
authors.lastname: Calon
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D007004:Hypoglycemic Agents; D007328:Insulin