Presentation: UND, NDSU, & ND-ACES bio and biomedical computation networking seminar
November 20, 2024, Alerus Center, Grand Forks, North Dakota
Immune-mediated mechanisms of progressive obesity, prediabetes, and cognitive impairment
Kai
Guo
Faculty Member
University of North Dakota
Co-authors: Sarah E. Elzinga, Postdoctoral, University of Michigan; Ali Turfah, Ph.D student, University of Michigan; Adam M. Allouch, Neurology Research Intern, University of Michigan; Dae Gyu Jang, Postdoctoral, University of Michigan; Rachel Parent, Research Staff, University of Michigan; Emily Glass, Laboratory Technician, University of Michigan; Geoffrey G. Murphy, Professor, University of Michigan; Stephen I. Lentz, Research Assistant Professor, University of Michigan; Kevin S. Chen, Clinical Assistant Professor, University of Michigan; Lili Zhao, Research Professor, University of Michigan; Junguk Hur, Associate Professor, UND; Eva L. Feldman, Professor, University of Michigan; Rosemary E. Henn, MD/PhD Doctoral Student, University of Michigan; Ian F. Webber-Davis, Laboratory Technician , University of Michigan; John M. Hayes, Research Lab Specialist Intermediate, University of Michigan; Crystal M. Pacut, Research Lab Specialist Senior, University of Michigan; Samuel J. Teener, Research Lab Tech Intermediate, University of Michigan; Andrew D. Carter, Research Lab Tech Intermediate, University of Michigan; Diana M Rigan, Research Lab Tech Intermediate, University of Michigan
Session
Poster Presentation
Metabolic stressors, such as obesity, metabolic syndrome, prediabetes, and diabetes, increase the risk of cognitive impairment, including Alzheimer's disease and related dementias (AD/ADRD). Immune dysregulation and inflammation may be key contributors to this risk, though the precise mechanisms remain unclear. We used a high-fat diet (HFD) mouse model to induce obesity, prediabetes, and cognitive impairment, tracking metabolic and cognitive changes alongside inflammatory markers and brain spatial transcriptomics. In parallel, we performed spatial transcriptomics and single-cell RNA sequencing on postmortem hippocampal tissue from AD and type 2 diabetes (T2D) patients. HFD causes progressive metabolic and cognitive decline, with significant inflammatory and neurodegenerative gene expression, particularly in glial cells, including microglia. Similar inflammatory and metabolic alterations were observed in human AD and T2D subjects, including shared upregulation of the pro-inflammatory gene SPP1. These findings suggest that metabolic stress drives cognitive impairment through inflammatory pathways, highlighting microglial SPP1's role in this process.