Growth, Characterization and Distribution of a Neurodegenerative Disease-Focused Fibroblast/iPS Cell Bank to Support Molecular Models of Patient-Specific Variation with Validation in Matched Donated Brain Tissues

Patients with clinical symptoms of dementia are a heterogeneous group that have multiple, often overlapping, causes of disease. Only evaluation of brain tissue at autopsy can provide a definitive diagnosis for most of these disorders. Notable exceptions include genetic diseases, although even then other age-related pathologies are common. Recently discovered techniques allow scientists to convert adult skin cells into stem cells (induced pluripotent stem cells, iPSCs) and to then use these iPSCs to generate human brain cells that are genetically matched to individual patients. These iPSC-derived cells hold immense promise as models for understanding molecular mechanisms and heterogeneity in neurodegenerative disease. However, accurate autopsy-based diagnosis is critical for these models to be reliable sources of information. Furthermore, scientific findings in iPSC-derived brain cells must be validated in human tissues, ideally matched to the iPSC donor. To address this issue, we have assembled a large bank of skin cell and iPSC lines matched to neurodegenerative disease patients and unaffected controls who have donated their brain tissues for research at the time of death. Each donated brain has undergone extensive characterization to provide an accurate diagnosis. This project seeks to grow, characterize and distribute this bank to the community of Alzheimer’s disease and dementia researchers around the world. We will focus on providing resources to study heterogeneity in neurodegenerative disease. Furthermore, we will generate iPSC-derived human neurons and distribute them to investigators, removing complex iPSC culture techniques as a barrier to research. Finally, we will perform phenotypic analysis of common Alzheimer’s disease markers in neurons from each line, providing a baseline measure of individual variation and allowing researchers to select cell lines with specific phenotypes for further study.