A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease

Guiquan Chen, Karen S. Chen, Jane Knox, Jennifer Inglis, Andrew Bernard, Stephen J. Martin, Alan Justice, Lisa McConlogue, Dora Games, Stephen B. Freedman, Richard G. M. Morris (Lead / Corresponding author)

Research output: Contribution to journalArticle

613 Citations (Scopus)

Abstract

Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.

Original languageEnglish
Pages (from-to)975-979
Number of pages5
JournalNature
Volume408
Issue number6815
DOIs
Publication statusPublished - 21 Dec 2000

Keywords

  • Aging
  • Alzheimer Disease/pathology
  • Amyloid beta-Peptides/metabolism
  • Animals
  • Disease Models, Animal
  • Hippocampus/pathology
  • Immunoenzyme Techniques
  • Learning Disorders/etiology
  • Maze Learning
  • Memory
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid

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    Chen, G., Chen, K. S., Knox, J., Inglis, J., Bernard, A., Martin, S. J., Justice, A., McConlogue, L., Games, D., Freedman, S. B., & Morris, R. G. M. (2000). A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature, 408(6815), 975-979. https://doi.org/10.1038/35050103