Mechanisms of neurotoxicity of amyloid aggregates
Alzheimer’s disease and related disorders are increasingly common degenerative disorders of the brain that occur in mid-to-late adult life. They cause impairments in memory and intellectual function, and lead to death within 10-15 years of diagnosis. 37 million people are affected by these diseases worldwide. They are the fourth leading cause of death among adults in industrialized societies and are becoming an increasingly significant healthcare problem in low- and middle-income countries.
Although we know that several genes and environmental effects can cause Alzheimer’s disease, we do not know why or how they lead to the death of nerve cells in the brain. The paucity of knowledge about the molecular mechanics of these diseases has hampered the development of sensitive and accurate tests and effective treatments.
The Alzheimer’s Disease consortium is a multidisciplinary team of research groups funded by a strategic neurodegeneration award from the Wellcome Trust and the MRC. Its members are from four distinct Universities: University of Cambridge, the University of Bristol, University of Toronto and the Max Planck Institute (Bonn) and the MRC Protein Phosphorylation Unit at the University of Dundee.
The consortium applies novel tools from physics, chemistry, computer science, genomics, biology and model organisms to generate a detailed understanding of the molecular mechanics that are activated by the accumulation of amyloid beta and tau, and that ultimately lead to the death of brain cells in Alzheimer’s Disease. The consortium aims to determine why and how both amyloid beta and tau accumulate in the brains of people with Alzheimer’s disease, and why the normal mechanisms for removing aggregated proteins from brain cells become overwhelmed. It also searches for and develops drug-like molecules that bind aggregation-prone proteins such as tau as potential therapies for these diseases.