Seattle Alzheimer’s Disease Brain Cell Atlas

Single Nucleus Transcriptomics

Cellular level transcriptomic data has the power to help uncover and understand cell type vulnerabilities in Alzheimer’s and related diseases.

Resources are provided to explore gene expression relationships in cell types of the middle temporal gyrus (MTG) and dorsolateral prefrontal cortex (DFC). For neurotypical reference brains and brains from the SEA-AD aged cohort that span the spectrum of Alzheimer’s disease, the SEA-AD Transcriptomics Comparative Viewer enables side by side comparison of gene expression in matched cells for any gene, comparison with essential donor metadata, and quantification of expression differences in MTG. The Transcriptomics Explorer shows the set of MTG brain cell types from younger neurotypical donors, illustrating the gene expression basis for defining cell types in the SEA-AD aged donor cohort. The new Allen Brain Cell (ABC) Atlas includes 2.78 million nuclei collected from both MTG and DFC and organized into a joint taxonomy to allow exploration of gene expression in the context of cell types and donor metrics.

Transcriptomics Comparative Viewer 

Transcriptomics Explorer (Reference MTG)

Allen Brain Cell (ABC) Atlas: Single Nucleus RNAseq Data (MTG and DFC)

The SEA-AD Gene Expression Trajectory Viewer application organizes more than 6 million sets of images to enable exploration of the trajectory of cell type-specific gene expression changes at multiple taxonomic levels in Alzheimer's disease. It relies on two key pieces of information:

Quantitative neuropathology: Donor brain tissue sections from the middle temporal gyrus (MTG) are stained for key pathological proteins and cell types of interest to Alzheimer’s disease. We use machine learning to quantify the staining on these images and define a single continuous pseudo-progression score that can order donors along a trajectory from least AD pathology to most AD pathology. View the data underlying these values in the 'Donors and Neuropathology' section below.

Gene expression: Single nucleus RNA-sequencing was collected for ~1.7 million cells from MTG (~1.2M post QC) and used to define 139 sets of cells with distinct gene expression profiles ("supertypes"). We compare gene expression levels in cells from each supertype with continuous pseudo-progression scores to identify gene expression changes in AD.

Gene Expression Trajectory Viewer

The MapMyCells application transforms cell types from a concept in publications to a tool for public research. MapMyCells allows users to map their single cell/nucleus transcriptomics data to high-quality reference taxonomy datasets developed through the BRAIN Initiative Cell Census Network and the SEA-AD consortium. MapMyCells automatically assigns cell types using thoroughly vetted state-of-the-art mapping algorithms to enable groundbreaking discoveries in neuroscience and Alzheimer’s disease research.

Apply The MapMyCells Tool To Your Data

Learn About MapMyCells

Tutorial: snRNA-seq Data From Human MTG

Chan Zuckerberg CELL by GENE: Visualize and explore gene expression and metadata from the SEA-AD study using Chan-Zuckerberg CELL by GENE. CZ CELLxGENE is a tool that helps scientists to explore and visualize high dimensional single-cell datasets in an interactive way, allowing them to surface important information that could lead to discoveries in treating disease. Currently, datasets spanning the full taxonomy and individual subclasses in both middle temporal gyrus (MTG) and dorsolateral prefrontal cortex (DFC) are available for exploration.

CZ CELLxGENE

Spatial Transcriptomics

The Allen Brain Cell (ABC) Atlas application provides a platform for visualizing multimodal single cell data across the mammalian brain and aims to empower researchers to explore and analyze multiple massive brain datasets simultaneously.

Explore the largest cell-resolution spatial transcriptomics (MERFISH) data set in human brain to date, which provides accurate spatial annotation and colocalization of cell types in the middle temporal gyrus (MTG) of 24 donors from the SEA-AD aged cohort that span the spectrum of Alzheimer’s disease. The spatial transcriptomics dataset can be viewed in parallel with the ~2.8 million cells collected from MTG and dorsolateral prefrontal cortex (DFC) using single nucleus transcriptomics and multiomics, and organized into a joint taxonomy to allow exploration of gene expression in the context of cell types and donor metrics (see “Single Nucleus Transcriptomics” section above).

Allen Brain Cell Atlas: MERFISH Data (MTG)

Allen Brain Cell Atlas: Home Page

Donors and Neuropathology

Review demographic, clinical, cognitive, and neuropathological information on the Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) cohort via the SEA-AD Donor Index. Data is derived from a full spectrum of aged donors, from healthy controls to those with high Alzheimer's disease pathology and dementia.

Examine images of donor brain tissue sections from multiple brain regions stained for key pathological proteins and cell types of interest to Alzheimer’s disease via the SEA-AD Neuropathology Image Viewer. Observe how quantitative measurements were made on stained tissue sections from the SEA-AD donors to assess pathological proteins, neuroinflammation, and neurodegeneration in middle temporal gyrus (MTG), medial entorhinal cortex (MEC), and hippocampus (HIP).

Data and specimens were obtained from the Adult Changes in Thought (ACT) Study from Kaiser Permanente Washington Health Research Institute (KPWHRI), and the University of Washington Alzheimer’s Disease Research Center (ADRC).

Donor Index

Neuropathology Image Viewer

Epigenomics: Chromatin Accessibility

Explore the open chromatin landscape and assess changes in chromatin accessibility as a function of Alzheimer's Disease neuropathological change by viewing single nucleus ATAC-seq data from the SEA-AD cohort in the UCSC Genome Browser. Browse this data from both middle temporal gyrus (MTG) and dorsolateral prefrontal cortex (DFC).

UCSC Genome Browser - ATAC-seq Data (MTG)

UCSC Genome Browser - ATAC-seq DATA (DFC)

Gene Knowledge Cards

The Gene Knowledge Cards application aggregates and summarizes data from the Allen Institute’s public single-cell transcriptomics datasets and historical atlases to highlight patterns of gene expression in the brain and identify other genes that are related in their expression. Users can explore how AD-associated genes are expressed in the brain in several contexts. Note that this application may be slow to load as it draws data from a significant number of sources.

Gene Knowledge Cards

Documentation, Data, and Downloads

Access to raw and processed data, quantifications, and documentation.

Documentation, Data, and Downloads