An increase in Aβ42 in the prefrontal cortex is associated with a reversal-learning impairment in Alzheimer's disease model Tg2576 APPsw mice

Jia Min Zhuo, Annamalai Prakasam, Melissa E. Murray, Hai Yan Zhang, Mark G. Baxter, Kumar Sambamurti, Michelle M. Nicolle

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The medial temporal lobe-dependent memory loss associated with Alzheimer's disease (AD) is often accompanied by a loss of prefrontal cortex-dependent cognitive domains that fall under the broad category of executive function. In this study, we examined the relationship between one type of prefrontal-dependent executive function, discrimination reversal-learning, and levels of the amyloid beta protein (Aβ) of 40 and 42 residues in a transgenic mouse model (Tg2576) of the over-expression of the familial AD mutant form of the amyloid precursor protein (APPsw). Tg2576 and their nontransgenic (NTg) littermates were assessed at 3 and 6 months of age when there is little to no amyloid plaque deposition. After reversal-learning assessment, Aβ40 and Aβ42 were quantified in the prefrontal cortex and hippocampus. Tg2576 mice were impaired in reversal-learning at 6 but not 3 months of age when compared to the NTg group. Coincidently, there was a corresponding approximately 3-fold increase of Aβ42 levels in the prefrontal cortex of 6- compared to 3-month-old Tg2576 mice. In addition, the prefrontal cortex contained higher levels of Aβ42 compared to the hippocampus at both 3 and 6 months of age, regardless of genotype, indicating a high vulnerability of this brain region to Aβ42 accumulation. These data suggest that the early emergence of reversal-learning deficits in the Tg2576 mouse may be due to the localized increase of Aβ42 in the prefrontal cortex.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalCurrent Alzheimer research
Volume5
Issue number4
DOIs
StatePublished - Aug 2008

Keywords

  • Amyloid precursor protein
  • Executive function
  • Learning errors
  • Perseverative errors

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'An increase in Aβ42 in the prefrontal cortex is associated with a reversal-learning impairment in Alzheimer's disease model Tg2576 APPsw mice'. Together they form a unique fingerprint.

Cite this