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iPSC Neurodegenerative Disease Initiative (iNDI)

A colorful visual representation of neurons.

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

The iNDI project team includes scientists in CARD’s Automated Cell Culture Expert Group, Proteomics Expert Group, and many other collaborators. Meet our team and learn more about CARD Expert Groups.

The iNDI team at CARD.
The iNDI team at CARD.

Visual Overview of the iNDI Project

Graphic showing the flow of the iNDI project, including the scope: gene and mutant identification, phase 1: identify iPSC and CRISPR, and phase 2: cell culture to break down and identify mutants and add to them data repository.
From Ramos DM et al., Tackling neurodegenerative diseases with genomic engineering: A new stem cell initiative from the NIH, Neuron,109 (7), 2021, 1080-1083, DOI:

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