title: Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent.
abstract: We recently generated an advanced mouse model of Alzheimer's disease (AD) by targeted knock-in of single-copy mutated human amyloid precursor-protein (APP) and tau genes, crossed with a non-symptomatic presenilin (PS1A246E) over-expressing mouse line. These PLB1Triple mice presented with age-dependent and AD-relevant phenotypes. Homozygous PLB1Triple mice aged 4-12 months were assessed here in a battery of spatial learning tasks: Exp.1 radial-arm water maze (spatial reference and working memory) Exp.2 open-field water maze (spatial reference memory); Exp.3 home cage observation system with spatial learning (IntelliCage); Exp.4 spontaneous object recognition (SOR; novel object and spatial object shift). A separate test with high-expression transgenic APP mice matching the design of experiment 1 was also performed. Spatial deficits in PLB1Triple mice were confirmed at 12, but not 4 months in both water maze tasks. PSAPP mice, by contrast, presented with severe yet non-progressive spatial learning deficits already at 4 months. During tests of spatial learning in SOR and IntelliCage, PLB1Triple mice neither acquired the location of the water-rewarded corner, nor recognize novel or spatially shifted objects at 4 months, indicating these protocols to be more sensitive than the water maze. Collectively and in line with AD symptomatology, PLB1Triple mice present with a graded and progressive age-dependent loss of spatial memory that can be revealed by the use of a battery of tasks. With the emergence of subtle deficits progressively increasing in severity, PLB1Triple mice may offer a more patho-physiologically relevant model of dementia than aggressive expression models.
authors.affiliation: School of Medical Sciences, College of Life Sciences and Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.
authors.forename: D
authors.initials: D
authors.lastname: Ryan
authors.forename: D
authors.initials: D
authors.lastname: Koss
authors.forename: E
authors.initials: E
authors.lastname: Porcu
authors.forename: H
authors.initials: H
authors.lastname: Woodcock
authors.forename: L
authors.initials: L
authors.lastname: Robinson
authors.forename: B
authors.initials: B
authors.lastname: Platt
authors.forename: G
authors.initials: G
authors.lastname: Riedel
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D053763:Presenilins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D053763:Presenilins; D016875:tau Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
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