iPSC Neurodegenerative Disease Initiative (iNDI)
The Induced Pluripotent Stem Cell Neurodegenerative Disease Initiative (iNDI) is a massive genome engineering project. iNDI researchers are engineering more than 100 genetic variants associated with Alzheimer’s and related dementias into cell models of disease. These cell models start as Induced Pluripotent Stem Cells (iPSCs) that can be grown into different brain cell types for genomic and proteomic studies. Any researchers can order from a large collection of cell lines.
Understanding which genes play a role in disease — and what role they play — may help identify new methods to prevent, delay, or treat dementia. Researchers have identified more than 70 genes that may contain variants that alter the risk for AD/ADRD based on human genetic studies.
To examine exactly how these genetic variants affect dementia risk, CARD scientists have used CRISPR/Cas9-based genetic engineering to create a cell line for each variant. Using these cell lines – along with state-of-the-art robotics to culture and examine hundreds of cell lines in parallel – CARD researchers are working to understand how each variant affects gene expression and cell behavior.
Harness iNDI Tools and Data
Researchers at CARD and collaborators are analyzing genomic and proteomic data from iNDI cell models to explore neurodegenerative disease mechanisms and identify new therapeutic targets. Explore iNDI-related protocols, tools, and data.
Access iNDI Cell Lines
We’ve created a foundational repository of isogenic-induced pluripotent stem cell (iPSC) lines using CRISPR/Cas9-based genetic engineering. Our goal is to create lines reflecting hundreds of variants across hundreds of genes relevant for Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, and other neurodegenerative disorders. All lines undergo rigorous quality control and are made publicly available to the research community. Learn more about accessing the iNDI cell line and plasmid repository.
Meet the iNDI Team
Visual Overview of the iNDI Project
Related Publications and News:
- A fully automated FAIMS-DIA mass spectrometry-based proteomic pipeline. Reilly L, et al. Cell Rep Methods. 2023. DOI: 10.1016/j.crmeth.2023.100593.
- A reference human induced pluripotent stem cell line for large-scale collaborative studies Pantazis. CB, et al. Cell Stem Cell. 2022. DOI: 10.1016/j.stem.2022.11.004.Ad
- iNDI Aims to Standardize Human Stem Cell Research. Alz Forum. 2021.
- CRISPRbrain: A data commons for functional genomics of neurodegenerative diseases. Paige Jarreau. CARD News. 2023.
- A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states. Drager et al. Nature Neuroscience. 2022. DOI: 10.1038/s41593-022-01131-4