Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer's disease

Patients with Alzheimer's disease (AD) suffer from impaired memory and emotional disturbances, the pathogenesis of which is not entirely clear. In APP/PS1 transgenic mice, a model of AD in which amyloid beta (A beta) accumulates in the brain, we have examined neurons in the lateral nucleus of the amygdala (LA), a brain region crucial to establish cued fear conditioning. We found that although there was no neuronal loss in this region and A beta plaques only occupy less than 1% of its volume, these mice froze for shorter times after auditory fear conditioning when compared to their non-transgenic littermates. We performed a three-dimensional analysis of projection neurons and of thousands of dendritic spines in the LA. We found changes in dendritic tree morphology and a substantial decrease in the frequency of large spines in plaque-free neurons of APP/PS1 mice. We suggest that these morphological changes in the neurons of the LA may contribute to the impaired auditory fear conditioning seen in this AD model. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.