Core F: Induced Pluripotent Stem Cell Core

PROJECT SUMMARY - INDUCED PLURIPOTENT STEM CELL (CORE F) Genome wide association studies (GWAS) have identified over 80 loci and candidate genes that are associated with altered risk of developing late-onset Alzheimer’s disease (AD). Similar approaches are also increasingly being used to identify loci associated with many other AD-Related Disorders (ADRD). Yet, precisely how these candidate genes impact the function of human cells to either promote or protect against the development or progression of AD/ADRD remains unclear. One promising approach that is increasingly being used by many in the field to examine such questions involves the use of induced pluripotent stem cells (iPSCs), which can be generated from control, AD, and ADRD participants and then differentiated into the key brain cells implicated in AD/ADRD. In 2013, the UCI Alzheimer’s Disease Research Center (ADRC) became the first Center in the network to establish a dedicated iPSC Core. Since then, the iPSC Core has generated over 400 AD/ADRD- related iPSC lines, including >120 CRISPR-edited isogenic pairs, and disseminated this unique resource to over 71 research groups around the world. In the current application, the iPSC Core will continue to embrace new advances in AD/ADRD genetics and CRISPR gene editing to generate and distribute additional highly unique iPSC lines generated from participants within the ADRC’s Clinical, Oldest-Old, and Down Syndrome Cores. Through four specific aims, the iPSC Core will employ innovative genetic studies and genome engineering to facilitate the study of genetic AD/ADRD risk factors across special populations (Aims 1, 2, 3), collaborate with AD/ADRD researchers worldwide (Aims 1-4), and educate the research and lay communities about the exciting scientific applications and implications of AD/ADRD iPSC research (Aim 4).