We are working to better understand the differences between healthy brains and brains affected by Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) at the cellular level. We are using single-cell sequencing technologies to create a human brain atlas or map of different brain cell types based on their gene activity. Researchers can use this atlas to investigate cell types present in brain regions affected in disease.
Alzheimer’s and related dementias are complex diseases involving many different pathways and cell types. Many different cells in a diseased brain experience change in their gene expression and downstream intracellular activities.
In the last 10 years, single-cell sequencing technologies have improved significantly, offering new ways to characterize cell types and study molecular profiles in health and disease. With state-of-the-art procedures and equipment for automated cell culture, microscopy, DNA and protein isolation, sequencing, and proteomics, CARD researchers can characterize gene activity within single cells and even within specific organelles in single cells.
The Single-Cell Sequencing Expert Group at CARD is looking at gene expression and chromatin accessibility (the degree to which certain areas of DNA are available for reading and translation into protein) in cells from both in vitro cultures and frozen tissues. In the future, they will also examine how gene expression varies in different subcellular compartments and spatial locations in the brain. These analyses of single-cell data will lead to a better understanding of AD/ADRD and the prioritization of potential target genes, pathways, and future therapeutics.
The samples CARD researchers analyze come from hundreds of ancestrally diverse individuals. We are committed to expanding the genetic diversity of samples to better understand the pathology of dementias and potential drug targets in understudied populations.
Access Brain Atlas Data
Access pipelines and perform workflows for single cell analysis with CARD’s open access data and research resources.
Meet the Brain Atlas Team
Related Publications and News:
Association of a common genetic variant with Parkinson’s disease is mediated by microglia. Langston et al. Science Translational Medicine. 2023. DOI: 10.1126/scitranslmed.abp8869
The Foundational Data Initiative for Parkinson Disease: Enabling efficient translation from genetic maps to mechanism. Bressan et al. Cell Genome. 2023DOI: 10.1016/j.xgen.2023.100261