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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

An Increase in Aβ42 in the Prefrontal Cortex is Associated with a Reversal-Learning Impairment in Alzheimers Disease Model Tg2576 APPsw Mice

Author(s): Jia-Min Zhuo, Annamalai Prakasam, Melissa E. Murray, Hai-Yan Zhang, Mark G. Baxter, Kumar Sambamurti and Michelle M. Nicolle

Volume 5 , Issue 4 , 2008

Page: [385 - 391] Pages: 7

DOI: 10.2174/156720508785132280

Price: $65


The medial temporal lobe-dependent memory loss associated with Alzheimers 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.

Keywords: Executive function, amyloid precursor protein, learning errors, perseverative errors

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