Grant: Project Grant

Alzheimer's disease (AD) is a common, progressive and ultimately lethal disease affecting ~5% of adults over 65 years of age and ~30% of adults over the age of 85 years in most Western societies. Both the prevalence and the annual expenditures on AD are expected to increase as the proportion of the population at risk increases over the next 20 years. The currently available treatments are of limited effectiveness as they target the symptoms of the disease but not the root cause. The major features of AD are accumulations of abnormal proteins called amyloid plaques and neurofibrillary tangles within the brain. Amyloid plaques appear as densely packed thread-like fibers that form around nerve cells and blood vessels. Evidence suggests that amyloid is highly toxic and is the primary cause of nerve cell death. Loss of these cells is the underlying event in AD and results in the clinical features of cognitive dysfunction and memory impairments. We have recently discovered a link between AD pathology and a family of proteins called, small ubiquitin-like modifiers (SUMOs). Our initial investigations have uncovered links between SUMO-related pathways and the development of Alzheimer disease plaques and tangles. This was made possible by the generation of novel animal models that combine SUMO and the key amyloid and tangle proteins. The ultimate objective of this research is to understand the cellular processes which cause AD and to use that information for the development of safe and effective treatments.