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

[ Vol. 5 , Issue. 4 ]

Author(s):

Jia-Min Zhuo, Annamalai Prakasam, Melissa E. Murray, Hai-Yan Zhang, Mark G. Baxter, Kumar Sambamurti and Michelle M. Nicolle   Pages 385 - 391 ( 7 )

Abstract:


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

Affiliation:

Wake Forest University,School of Medicine, Winston-Salem, NC 27157, USA.



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