Alzheimer’s disease (AD) is a leading cause of death today in Western Europe and North America. Therefore it is a major challenge for medical research. At present, its genesis is still largely unknown and no cure or effective treatment is available.
The Amyloid Precursor Protein is a membrane protein present at the synapse of neurons. During the protein recycling process, the transmembrane domain of APP is cleaved and releases small fragments of different lengths (Aβ). Their deposition in brain tissue is an early indicator of Alzheimer’s disease.
The experimental characterization of the transmembrane region of APP (APP-TM) has revealed several contradictory structures. At the EPFL, I combined molecular dynamics and metadynamics simulations to show that the APP-TM region is highly flexible and can readily respond to the lipid environment. The size of the embedding detergent micelles used in the experimental set-up strongly affected the hydration and conformation of the APP-TM.