title: Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.
abstract: Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-β-amyloid antibody. Our data suggest a biomarker strategy for the early detection of β-amyloid-related abnormalities.
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
authors.forename: V
authors.initials: V
authors.lastname: Beglopoulos
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
authors.forename: J
authors.initials: J
authors.lastname: Tulloch
authors.affiliation: Department of Neurology, Mass General Institute for Neurodegeneration, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Roe
authors.affiliation: Neuroscience Paris Seine, Institut de Biologie Paris Seine, Sorbonne Universités, Pierre and Marie Curie University, UM CR18, INSERM U1130, CNRS UMR 8246, 75005 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Daumas
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.|Department of Dietetics, Nutrition and Biological Sciences, School of Health Sciences, Queen Margaret University, Musselburgh EH21 6UU, UK.
authors.forename: L
authors.initials: L
authors.lastname: Ferrington
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Watson
authors.affiliation: Department of Neurology, Mass General Institute for Neurodegeneration, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Neurology, Mass General Institute for Neurodegeneration, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
authors.forename: P A T
authors.initials: PA
authors.lastname: Kelly
authors.affiliation: Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson &Johnson, 3210 Merryfield Row, San Diego, California 92121, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bard
authors.affiliation: Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.|Instituto de Neurociencias, CSIC-UMH, San Juan de Alicante 03550, Spain.
authors.forename: R G M
authors.initials: RG
authors.lastname: Morris
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001931:Brain Mapping; D003847:Deoxyglucose / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D057134:Antibodies, Neutralizing; D015415:Biomarkers; D003847:Deoxyglucose; D005947:Glucose