title: Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer's disease.
abstract: The 5XFAD mice are an early-onset transgenic model of Alzheimer's disease (AD) in which amyloid plaques are first observed between two and four months of age in the cortical layer five and in the subiculum of the hippocampal formation. Although cognitive alterations have been described in these mice, there are no studies that focused on the onset of hippocampus-dependent memory deficits, which are a hallmark of the prodromal stage of AD. To identify when the first learning and memory impairments appear, 5XFAD mice of two, four, and six months of age were compared with their respective wild-type littermates using the olfactory tubing maze, which is a very sensitive hippocampal-dependent task. Deficits in learning and memory started at four months with a substantial increase at six months of age while no olfactory impairments were observed. The volumetric study using magnetic resonance imaging of the whole brain and specific areas (olfactory bulb, striatum, and hippocampus) did not reveal neuro-anatomical difference. Slight memory deficits appeared at 4 months of age in correlation with an increased astrogliosis and amyloid plaque formation. This early impairment in learning and memory related to the hippocampal dysfunction is particularly suited to assess preclinical therapeutic strategies aiming to delay or suppress the onset of AD.
authors.affiliation: Aix Marseille Université, CNRS, NICN, UMR7259, Marseille, France.
authors.forename: Stéphane D
authors.initials: SD
authors.lastname: Girard
authors.forename: Marlyse
authors.initials: M
authors.lastname: Jacquet
authors.forename: Kévin
authors.initials: K
authors.lastname: Baranger
authors.forename: Martine
authors.initials: M
authors.lastname: Migliorati
authors.forename: Guy
authors.initials: G
authors.lastname: Escoffier
authors.forename: Anne
authors.initials: A
authors.lastname: Bernard
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
authors.forename: François
authors.initials: F
authors.lastname: Féron
authors.forename: Santiago
authors.initials: S
authors.lastname: Rivera
authors.forename: François S
authors.initials: FS
authors.lastname: Roman
authors.forename: Evelyne
authors.initials: E
authors.lastname: Marchetti
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000503:physiopathology / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000473:pathology; D009929:Organ Size; D058225:Plaque, Amyloid / Q000209:etiology / Q000473:pathology; D017354:Point Mutation; D053764:Presenilin-1 / Q000235:genetics; D012903:Smell / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: amyloid plaques; behavioral assessment; gliosis; hippocampus; olfactory tubing maze