Synaptic alterations in mouse models for Alzheimer disease—A special focus on N-truncated abeta 4-42

Abstract

This commentary reviews the role of the Alzheimer amyloid peptide Aß on basal synaptic transmission, synaptic short-term plasticity, as well as short- and long-term potentiation in transgenic mice, with a special focus on N-terminal truncated Aß4-42. Aß4-42 is highly abundant in the brain of Alzheimer’s disease (AD) patients. It demonstrates increased neurotoxicity compared to full length Aß, suggesting an important role in the pathogenesis of AD. Transgenic Tg4-42 mice, a model for sporadic AD, express human Aß4-42 in Cornu Ammonis (CA1) neurons, and develop age-dependent hippocampal neuron loss and neurological deficits. In contrast to other transgenic AD mouse models, the Tg4-42 model exhibits synaptic hyperexcitability, altered synaptic short-term plasticity with no alterations in short- and long-term potentiation. The outcomes of this study are discussed in comparison with controversial results from other AD mouse models.