APP-mediated mechanical signaling and its regulation by Alzheimer’s risk genes

We recently discovered that Amyloid Precursor Protein (APP) is connected to the force-generation machinery in neurons and so this project will test the hypothesis that APP is under tension, part of th

Our preliminary data revealed for the first time that APP is connected to the force-generation machinery via its interaction with a protein called talin, combined with the known capacity of APP molecules to interact together this immediately indicated a new role for APP as a tension-bearing linkage and a mechanical sensor (where its cleavage in healthy brains is used as signals to maintain synaptic health). This provides a big hypothesis of a mechanical basis of Alzheimer’s Disease, where disruption of the mechanics of the neurons contributes to the mis-processing of APP and the formation of a

If we can prove that APP is a force-bearing molecule and under tension, this will transform the field of Alzheimer’s Disease as we will show a role for APP that is novel, and identify a new cause of the disease. The mechanical signaling machinery that would be maintaining this linkage is well studied in diseases like cancer. We predict that this study will validate a new therapeutic approach for treating Alzheimer’s by targeting neuronal mechanics to slow the spread, and there are a wide range of drugs already on the market for treating cellular mechanics in other diseases.