Texas A&M University
Title: Islet amyloid polypeptide (IAPP) association with Alzheimer's Disease pathology and diagnosis
Dr. Murray joined St. George’s University in January, 2014 as an Associate Professor in the School of Medicine, Department of Physiology and Neuroscience. He is currently Program Director for "Medical Student Assessment Program -MSAP". Dr. Murray also teaches on various undergraduate Arts & Sciences course, and Medical Physiology. In addition to teaching, Dr. Murray is conducting research projects on Alzheimer's disease in Grenada, and EEG analysis of learning and memory. Dr. Murray received a BSc. Hons Co-op in Biology from the University of Waterloo, Canada. As part of his undergraduate co-operative programme, Dr. Murray conducted 1.5 years of research at Dept Fisheries and Oceans, Merck Fross and Pioneer Hi-Bred in aquatic ecosystems, pharmacological evaluation of asthma compounds, and genetic manipulation of food crops. He completed a Ph.D. in Physiology at McGill University. His PhD research brought together his two main interests, protein folding, and metabolic dysfunction (diabetes and obesity). As a Postdoctoral Researcher, and Research Associate at the University of Pennsylvania for several years, he made seminal discoveries in Parkinson's and Alzheimer's diseases. These discoveries centered on n protein misfolding mechanisms. At Texas A&M Health Science Center, he continued his research on Alzheimer's disease, merging his Ph.D. and Postdoctoral interests; protein misfolding and metabolic dysfunction. Research awards include: National Sciences & Engineering Research Council of Canada (NSERC), Industrial Undergrad Student research Awards, Pioneer Hi-Bred- 1992-1993; Research day awards at McGill University; Renouf Fellowship, Quebec Black Medical Association Conference, 1st Place for Oral Presentation 1998; Colonel Renouf Award 1995-1996 and Research Institute Fund 1997-1998, Royal Victoria Hospital, Endowment award ; CNDR Annual Retreat, Univ. Pennsylvania 1st Place for Poster Presentation 2000;Texas A&M HSC Class of 2015 outstanding achievement for teaching.
Amyloid formation is the pathological hallmark of type 2 diabetes (T2D) and Alzheimer's disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) in the pancreas and amyloid β (Aβ) in the brain. Since it has been shown that IAPP enters the brain and that disparate amyloids can cross-seed each other to augment amyloid formation, we determined if such cross-seeding can occur with the amyloids involved in T2D and AD. We demonstrated that: (1) IAPP promoted oligomerization of Aβ in vitro and in silico, (2) peripheral injection of IAPP increased murine brain IAPP levels, (3) endogenous IAPP localized to Aβ in plaques in mouse models of AD, (4) IAPP was present in and secreted from astrocytes, and (5) IAPP levels were elevated in AD cerebrospinal fluid (CSF). These observations prompted us to explore a potential mechanism whereby IAPP elevated during metabolic dysfunction enters the brain to cross-seed Aβ and augment AD pathology. We tested this mechanism in both humans and transgenic mice, correlating peripheral levels of IAPP with AD pathology. In African Americans, a group with increased risk for both T2D and AD, peripheral IAPP levels were not significantly different in samples with no disease, T2D, AD, or both T2D and AD. Furthermore, in the Tg2576 AD mouse model, IAPP plasma levels were not significantly elevated at an age where the mice exhibit the glucose intolerance of pre-diabetes. Based on this data, it appears unlikely that peripheral IAPP cross-seeds Aβ pathology in AD brain. However, we provide evidence for a novel association between brain derived IAPP and AD, which suggests that brain derived IAPP plays a role in Aβ oligomerization and AD pathology. This potential connection, along with IAPP's known role in weight and memory loss, requires further research.