The goal of this proposal is to investigate how one of the recently identified late-onset Alzheimer’s disease risk genes, namely BIN1, contributes to neuropathology. BIN1 is an adaptor protein that regulates membrane dynamics in a variety of cellular contexts. Only limited information is available on BIN1 expression and function in the brain. As such, there is much to be learned about the precise biological and mechanistic connection between BIN1 and Alzheimer’s disease. We propose to use an integrated approach employing cultured cells and BIN1 transgenic mice to test specific hypotheses regarding BIN1 function and dysfunction in Alzheimer’s disease.