Cellular and Molecular Life Sciences

, Volume 70, Issue 14, pp 2603–2619

Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent

  • D. Ryan
  • D. Koss
  • E. Porcu
  • H. Woodcock
  • L. Robinson
  • B. Platt
  • G. Riedel
Research Article

DOI: 10.1007/s00018-013-1314-4

Cite this article as:
Ryan, D., Koss, D., Porcu, E. et al. Cell. Mol. Life Sci. (2013) 70: 2603. doi:10.1007/s00018-013-1314-4

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.

Keywords

Knock-in mouseAmyloidTauSpatial cognitionLearningMemory

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • D. Ryan
    • 1
  • D. Koss
    • 1
  • E. Porcu
    • 1
  • H. Woodcock
    • 1
  • L. Robinson
    • 1
  • B. Platt
    • 1
  • G. Riedel
    • 1
  1. 1.School of Medical Sciences, College of Life Sciences and Medicine, Institute of Medical SciencesUniversity of AberdeenAberdeenScotland, UK