Abstract #3052

Studying the Impact of Diabetes on the Pathogenesis of Alzheimer’s Disease

Thomas Jue¹, James Graham², Usman Rehman¹, Keshav Datta³, Shie-Chau Liu³, Jane Chen⁴, Ralph Hurd³, and Daniel Spielman³

¹Biochemistry and Molecular Medicine, University of California, Davis, CA, United States, ²Nutrition, University of California, Davis, CA, United States, ³Radiology, Stanford University, Stanford, CA, United States, ⁴Center for Genomic Pathology Laboratory, University of California, Davis, CA, United States

Synopsis

Keywords: Alzheimer's Disease, Neurodegeneration, Hyperpolarized C13 MRI/MRS Metabolism

How type 2 diabetes (T2D) increases the risk of Alzheimer’s disease (AD) frames the central research question. The study has developed a rat model that exhibits both T2D and AD (T2D-AD +/-). These hemizygous animals contain the genes APPswe and PS1ΔE9 and display amyloid burden as early as 6 mos of age. Standard Tg344-AD +/- model shows amyloid plaque at 9 mos of age.

AD impairs cognitive performance but brain metabolism as observed with Barnes Maze test and dynamic nuclear polarization experiments. MRS/MRI and physiological studies can now use the animal model to interrogate how insulin insensitivity accelerates AD onset/progression.

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