Various animal models of
Alzheimer's disease (AD) have been created to assist our appreciation of AD pathophysiology, as well as aid development of novel therapeutic strategies. Despite the discovery of mutated
proteins that predict the development of AD, there are likely to be many other
proteins also involved in this disorder. Complex physiological processes are mediated by coherent interactions of clusters of functionally related
proteins. Synaptic dysfunction is one of the hallmarks of AD. Synaptic
proteins are organized into
multiprotein complexes in high-density membrane structures, known as
lipid rafts. These microdomains enable coherent clustering of synergistic signaling
proteins. We have used mass analytical techniques and multiple bioinformatic approaches to better appreciate the intricate interactions of these multifunctional
proteins in the 3xTgAD murine model of AD. Our results show that there are significant alterations in numerous receptor/cell signaling
proteins in cortical
lipid rafts isolated from 3xTgAD mice.