SEA‐AD: Scientific analysis and open access resources targeting early changes in Alzheimer’s disease
Authors: Miller Jeremy A , Hawrylycz Michael J , Aitken Matthew , Ariza Jeannelle , Chakrabarty Rushil , Ding Song‐Lin , Ding Yi , Ferrer Rebecca , Goldy Jeff , Gratiy Sergey , Guilford Nathan , Guzman Junitta , Kaplan Eitan S , Mei Nicholas , Melief Erica J , Nyhus Julie , Pham Thanh , Rachleff Victoria M , Samson Jake , Smith Kimberly , Torkelson Amy , Travaglini Kyle J , Wakeman Wayne , Close Jennie , Crane Paul K , Darvas Martin , Gabitto Mariano I , Grabowski Thomas J , Hodge Rebecca D , Jayadev Suman , Latimer Caitlin S , Levi Boaz P , Long Brian , MacDonald Christine , Mukherjee Shubhabrata , Larson Eric B , Keene C. Dirk , Lein Ed S 
Published: June 2023

Background

Alzheimer’s disease (AD) is the most common form of dementia, representing ∼70% of all dementia cases, and affecting much of the aged population. Currently our understanding of AD neuropathology is largely centered on characteristic deposition of certain neuropathological proteins and identification of histologically defined neuronal populations. Molecular tools to characterize the transcriptome, epigenome, and spatial organization of single cells in complex brain tissues allow a more refined look at how the neurotypical brain changes in AD than had been possible previously. Linking molecular, cellular, genomic, cognitive, and pathological indicators of AD progression will be essential for understanding disease mechanisms.

Methods

The Seattle Alzheimer’s Disease Brain Cell Atlas (SEA‐AD) brings together experts in AD research and large‐scale molecular/anatomical brain mapping to modernize AD tissue banking methods, and to combine traditional and quantitative neuropathology with emerging genotyping, single nucleus transcriptomics, single nucleus epigenomics, and spatial transcriptomics technologies. Applied to multiple brain regions in donors spanning different stages of AD pathology, these techniques will identification of cell type specific molecular pathways and yield valuable insights into selective vulnerability or resistance to pathology. Two well characterized cohorts (Adult Changes in Thought (ACT) and the University of Washington ADRC) provided 84 subjects of varying degrees of AD severity, including cognitively normal subjects.

Results

The initial focus of SEA‐AD was on integrating and interpreting relationships between all collected multimodal data in middle temporal gyrus (MTG). Identified cell types and molecular pathways of interest are presented separately and are both consistent with and expand upon results found from ROSMAP and other cohorts. The complete SEA‐AD MTG atlas is now freely and publicly available at brain‐map.org and includes access to all data and associated donor metadata, tools for visualization and exploration of molecular data, exploration of pathology images, a tool for assigning cell types to community‐based ‐omics datasets, comprehensive documentation, and user support.

Conclusions

SEA‐AD has developed a high resolution, high‐quality, publicly accessible atlas of aging and AD, and is designed to better understand the complex and likely heterogenous nature of AD.