title: F-spondin gene transfer improves memory performance and reduces amyloid-β levels in mice.
abstract: Alzheimer's disease (AD) is the most prevalent form of dementia affecting the elderly. Evidence has emerged signifying that stimulation of the reelin pathway should promote neural plasticity and suppress molecular changes associated with AD, suggesting a potential therapeutic application to the disease. This was explored through the use of lentiviral vector-mediated overexpression of the reelin homolog, F-spondin, which is an activator of the reelin pathway. Intrahippocampal gene transfer of F-spondin improved spatial learning/memory in the Morris Water Maze and increased exploration of the novel object in the Novel Object Recognition test in wild-type mice. F-spondin overexpression also suppressed endogenous levels of amyloid beta (Aβ(42)) in these mice and reduced Aβ plaque deposition while improving synaptophysin expression in transgenic mouse models of AD. These data demonstrate pathologic and cognitive improvements in mice through F-spondin overexpression.
authors.affiliation: Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Hafez
authors.forename: J Y
authors.initials: JY
authors.lastname: Huang
authors.forename: J C
authors.initials: JC
authors.lastname: Richardson
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: D A
authors.initials: DA
authors.lastname: Peterson
authors.forename: R A
authors.initials: RA
authors.lastname: Marr
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D000091042:Reelin Protein
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016326:Extracellular Matrix Proteins; C552523:F-spondin protein, mouse; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D000091042:Reelin Protein; C075222:amyloid beta-protein (1-42); D049452:Green Fluorescent Proteins; C000717127:RELN protein, human; C000717128:Reln protein, mouse