The Alzheimer’s Disease Research Center (ADRC) supports laboratory science projects investigating the underlying mechanisms of Alzheimer's disease with the goal of using these insights to inform the development of improved diagnostics and more effective treatments. The ADRC is currently supporting three funded translational projects.
Cognitive and Biological Profiling of Elders with Diabetes
Diabetes and Alzheimer’s disease (AD) are both common diseases that occur more frequently as we age and are associated with significant cognitive problems. This study—called the Memory and Diabetes Study (MADS)— explores how diabetes affects cognitive function by looking at older diabetic minority participants without dementia. We are collecting cognitive data and biomarkers related to diabetes, inflammation, and AD and vascular neuropathology in order to explore relationships between cognitive impairment and diabetes.
Principal Investigator: Corbett Schimming, MD, Assistant Professor of Psychiatry
Insulin Signaling and Action in the Alzheimer Brain and in iPSC-Derived Human Brain Cells
Researchers suspect that the association of diabetes and AD has to do with the body’s responsiveness to the effects of insulin in AD patients. This study uses induced pluripotent stem cell (iPSC) derived from patients with AD to generate neurons, astrocytes, mixed brain cell cultures, and white adipocytes to study whether there are cell inherent differences in insulin signaling and insulin action. We will further examine if insulin resistance plays a role in the pathology causing or predisposing to cognitive impairment or AD to test the hypothesis that insulin resistance is a consistent feature and important for AD progression.
Principal Investigator: Christoph Buettner, MD, PhD, Associate Professor of Medicine, Endocrinology, Diabetes and Bone Disease and Associate Professor of Neuroscience
Effects of Type 2 Diabetes (T2D) and Alzheimer Disease (AD) on Angiogenesis and Angiogenic Complexes
Vascular disorders affect transport of nutrients and oxygen to neurons and this is believed to increase the risk of AD. Through angiogenesis, the body generates new blood vessels from pre-existing vasculature and we hypothesize that there may be insufficient angiogenesis in the brains of individuals with AD. Type 2 diabetes (T2D) is also associated with vascular abnormalities in the brain that may provide etiological links between T2D and AD. In this project we examine whether AD and T2D impair brain neovascularization in response to ischemic injury and whether formation of angiogenic complexes is affected by AD and T2D. In addition, we examine whether these complexes are affected by AD and T2D in human brains. We also ask whether peptide ephrinB2/CTF2, the product of gamma secretase cleavage of ephrinB2 that we found that promote angiogenesis in vitro, promotes neovascularization in vivo and whether it acts as a protective factor against vascular impairments in AD and T2D.
Principal Investigator: Yonejung Yoon, PhD, Postdoctoral Fellow