Elucidating how Amyloid-Beta Changes Protein Expression in AD Brain

We propose to study the functional consequences of a transcription factor complex that specifically forms in AD and deregulates protein expression in AD brain.Aim 1: We found that the Aß1-42-induced interaction of two transcription factors is part of AD pathology. Here, we will investigate whether the formation of this complex is sufficient to dysregulate intracellular protein trafficking, and whether as a consequence Aß1-42 production is increased. Aim 2: We propose that AD-linked transcription factor interaction dysregulates the expression of genes important for the secretion of proteins in AD brain. Here, we will investigate the consequences of neuron-specific loss of one of the transcription factors in wildtype mice and in an AD mouse model.