Early changes in Aβ levels in the brain of APPswe transgenic mice—Implication on synaptic density, α7 neuronal nicotinic acetylcholine- and N-methyl- d-aspartate receptor levels

Abstract

Tg 2576 (APPswe) mice develop age-related amyloid deposition as well as behavioural- and electrophysiological changes in the brain. In this study, APPswe mice were investigated from 7 to 90 days of age. We observed high Aβ levels in the cortex of APPswe mice at 7 days of age, suggesting that these mice produce Aβ from birth. A positive correlation between Aβ and synaptophysin levels, followed by changes in ERK MAPK activity, indicated that Aβ causes altered synaptic function and an increase in the number of synaptic terminals. In addition, alterations in [ 125I]αbungarotoxin- and [ 3H]MK-801 binding sites were also observed in APPswe mice compared to controls. In conclusion, over-expression of Aβ early in life causes changes in synaptophysin levels and number of [ 125I]αbungarotoxin- and [ 3H]MK-801 binding sites. The results may provide important information about the onset and consequences of Aβ pathology in this transgenic mouse model.