Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice

Brian J. Hock, K. Matthew Lattal, Laura Shapiro Kulnane, Ted Abel, Bruce Lamb

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To gain insight into the relationship between pathological alterations and memory deficits observed in Alzheimer's disease (AD), a number of amyloid precursor protein (APP) transgenic animal models have been generated containing familial AD mutations. The most commonly utilized method involves a cDNA-based approach, utilizing heterologous promoters to drive expression of specific APP isoforms. As a result of the assumptions inherent in the design of each model, the different cDNA-based transgenic mouse models have revealed different relationships between the biochemical, pathological and behavioral alterations observed in these models. Here we provide further characterization of a genomic-based, amyloid precursor protein yeast artificial chromosome transgenic mouse model of AD, R1.40, that makes few assumptions regarding disease pathogenesis to study the relationship between brain pathology and altered behavior. Aged R1.40 transgenic and control mice were tested for learning and memory in the Morris water maze and for working memory in the Y maze. Results from the water maze demonstrated intact learning in the both control and R1.40 mice, but impairments in the long-term retention of this information in the transgenic mice, but not controls. Interestingly, however, long-term memory deficits did not correlate with the presence of Aβ deposits within the group of animals examined. By contrast, age-related working memory impairments were also observed in the Y maze in the R1.40 mice, and these deficits correlated with the presence of Aβ deposits. Our results demonstrate unique behavioral alterations in the R1.40 mouse model of AD that are likely both dependent and independent of Aβ deposition.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalCurrent Aging Science
Volume2
Issue number3
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Memory Disorders
Transgenic Mice
Alzheimer Disease
Genome
Pathology
Short-Term Memory
Complementary DNA
Learning
Yeast Artificial Chromosomes
Genetically Modified Animals
Long-Term Memory
Water
Amyloid
Protein Isoforms
Animal Models
Mutation
Brain

Keywords

  • Aβ deposits
  • Alzheimer's disease
  • APP
  • Learning
  • Memory
  • Transgenic mice

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice. / Hock, Brian J.; Lattal, K. Matthew; Kulnane, Laura Shapiro; Abel, Ted; Lamb, Bruce.

In: Current Aging Science, Vol. 2, No. 3, 2009, p. 205-213.

Research output: Contribution to journalArticle

Hock, Brian J. ; Lattal, K. Matthew ; Kulnane, Laura Shapiro ; Abel, Ted ; Lamb, Bruce. / Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice. In: Current Aging Science. 2009 ; Vol. 2, No. 3. pp. 205-213.
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