Gary E. Gibson

Our goal is to better understand Alzheimer’s disease (AD) and to develop new therapies. Our research strategy is to use autopsy brains and living cells to identify novel, clinically relevant abnormalities (e.g., abnormalities in calcium, thiamine dependent enzymes and mitochondrial enzymes) that provide a foundation to understand the mechanism of changes in brain. We then model the abnormalities with proteins, cells (including stem cells and animals) to understand the underlying mechanisms and to develop new therapeutic approaches. 

Our most recent studies indicate that post-translational modification translates metabolic dysfunction to brain dysfunction and pathology. Thiamine (vitamin B1) dependent enzymes are diminished in tissues from AD patients, and interfering with thiamine dependent enzymes exacerbates plaque formation, phosphorylation of tau, and the calcium changes that occur in cells from AD patients or animal models of AD. 

Our recent studies focus on thiamine (vitamin B1) dependent post-translational modifications, including glycation, acetylation and succinylation which are critical in AD. Defining the significance of these hundreds of modifications will be critical to understanding Alzheimer’s disease. Thus, treating the thiamine deficit and reversing these changes is an attractive therapeutic approach.  Increasing thiamine to pharmacologic levels with the thiamine prodrug benfotiamine is very protective AD models and produced encouraging results in a pilot trial with AD patients. An ongoing project expands the studies to 46 centers around the US.