اختلال آموزش معکوس تبعیض اولیه و یادگیری فضایی حفظ شده در یک مطالعه طولی از موش Tg2576 APPsw

To understand the relationship between amyloid-β 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 C57B6 × SJL F1 mice are most pronounced on putative frontal cortex-dependent tasks and that increasing Aβ load only affects discrimination reversal learning in our study.

Tg2576 mice, which over-express the human APP Swedish mutation (K670N, M671L), are widely studied as an Alzheimer's disease (AD) transgenic mouse model [23]. This transgenic model develops a pathological hallmark of AD with increasing age, Aβ plaque deposition. Amyloid plaques are distributed in cortical and hippocampal regions after 10 months of age in a pattern similar to that observed in humans [24] and [50]. Levels of Aβ 1–40 and 1–42 also increase prior to plaque deposition, with measurable levels apparent by 6–8 months of age [24] and [53]. Age-dependent memory loss has been observed in Tg2576 mice [26] and [53], and some studies argue that the cognitive impairment is associated with soluble brain Aβ [27], [32] and [53].