Structure of Abeta C-Terminal Domain in Toxic Oligomers

Progress Updates

The seminal event in Alzheimer’s disease is the clustering of sticky protein fragments into small particles that are toxic to brain cells. Dr. Tessier’s team is basing their project on their recent discovery that the Alzheimer’s protein can form two types of particles of identical size, yet only one of them is toxic to brain cells. In the first year of this study, the team has developed new methods for investigating the structure of both types of protein particles to understand why only one type is toxic. They find that the stickiest regions of the Alzheimer’s protein are exposed on the surface of the toxic particles, while these same regions are shielded within the core of the non-toxic particles. Moreover, they find that the toxic Alzheimer’s particles are unusually effective at disrupting “membranes” (the packaging that keeps cells intact) that are similar to the outer wall of brain cells, while non-toxic particles are unable to disrupt such membranes. Dr. Tessier’s team suggests their results show that toxic Alzheimer’s particles have sticky surfaces that are able to interact with and disrupt brain cells, leading to cell death and loss of brain function. They expect that the methods they have developed for studying the structure of Alzheimer’s protein particles will be useful for identifying toxic particles in many other scientific studies of Alzheimer’s disease. Moreover, their findings suggest that drugs targeting the sticky patches of the Alzheimer’s protein may be most effective at preventing the toxicity of Alzheimer’s protein particles.