Toxic proteins, known as ‘plaques’ and ‘tangles’ accumulate in the brains of Alzheimer’s disease patients. The protein that makes up the plaques, known as amyloid-β, appears to have a particularly toxic ingredient, which is called ‘pyroglutamylated amyloid β’. This protein appears to work together with the protein present in the tangles, known as ‘hyperphosphorylated tau’, to produce the clinical symptoms associated with Alzheimer’s disease. It may also have an effect on the protein associated Lewy body diseases, known as alpha synuclein.
What our current research aims to find out is how pyroglutamylated Aβ is involved in the mechanisms that cause Alzheimer’s disease and Lewy body diseases. Using tissue taken from the Newcastle Brain Tissue Resource, we use stains to work out how pyroglutamylated Aβ is found in the brains of Alzheimer’s disease and Lewy body disease cases, and how it compares to hyperphosphorylated tau and α- synuclein. We then compare these findings to clinical information recorded from the patients during life. In addition, we’ll examine pyroglutamylated Aβ in human CSF, the fluid found in the brain and spine to see whether the levels compare with that found in the brain. If it does, this may help doctors in diagnosis, and potentially help us find us find treatments, for dementia.
This project is led by Dr Lauren Walker and funded by the Alzheimer's Society.