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

Cell Mol Life Sci. 2013 Jul;70(14):2603-19. doi: 10.1007/s00018-013-1314-4. Epub 2013 Mar 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Brain / pathology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Disease Models, Animal
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Male
  • Maze Learning / physiology*
  • Memory
  • Mice
  • Mice, Transgenic
  • Presenilins / genetics
  • Presenilins / metabolism
  • Promoter Regions, Genetic
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • Amyloid beta-Protein Precursor
  • Presenilins
  • tau Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2