Early discrimination reversal learning impairment and preserved spatial learning in a longitudinal study of Tg2576 APPsw mice.
To understand the relationship between amyloid-beta and cognitive decline in Alzheimer's disease, we evaluated cortical and hippocampal function in a transgenic mouse model of amyloid over-expression in Alzheimer's disease, the Tg2576 mouse. Tg2576 mice and their non-transgenic littermates were assessed at both 6 and 14 months of age in a battery of cognitive tests: attentional set-shifting, water maze spatial reference memory and T-maze working memory. Spatial reference memory was not affected by Tg status at either age. Working memory was only affected by age, with 6-month-old mice performing better than 14-month-old ones. Older mice were also significantly impaired on reversal learning and on the intra- and extra-dimensional shift in attentional set-shifting. A significant transgene effect was apparent in reversal learning, with Tg2576 mice requiring more trials to reach criterion at 6 months old. These data indicate that the effects of normal aging in C57B6xSJL F1 mice are most pronounced on putative frontal cortex-dependent tasks and that increasing Abeta load only affects discrimination reversal learning in our study.
Zhuo
Jia-Min
JM
College of Medicine, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA. zhuo.jiamin@mayo.edu <zhuo.jiamin@mayo.edu>
Prescott
Sonya L
SL
Murray
Melissa E
ME
Zhang
Hai-Yan
HY
Baxter
Mark G
MG
Nicolle
Michelle M
MM
D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000502:physiology; D001522:Behavior, Animal; D004193:Discrimination Learning / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007859:Learning Disabilities / Q000209:etiology* / Q000235:genetics; D008137:Longitudinal Studies; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D012193:Reversal Learning / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor