SEA-AD is a multimodal cellular atlas and resource for Alzheimer's disease

Abstract

The Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) is a multifaceted open data resource designed to identify cellular and molecular pathologies that underlie Alzheimer’s disease. Integrating neuropathology, single cell and spatial genomics, and longitudinal clinical metadata, SEA-AD is a unique resource for studying the pathogenesis of Alzheimer’s and related dementias.

Fig. 1|. SEA-AD project study design.

SEA-AD workflow integrates molecular standards, image-based neuropathology, clinical metadata and modeling of disease trajectory to produce a new atlas of AD. a. Donor selection through ADRC and ACT enables a multiregion profile across a diverse cohort. b. Machine-learning automated tissue parcellation and quantification. c. Neuropathology and molecular characterization using single-cell methods, d. Statistical modeling of continuous pseudo-time disease severity and progression, e. Brain-wide single-cell molecular atlases developed through BICAN provide a framework for comparison and analysis in AD. f, BICAN taxonomy is expanded to include disease-modified cell types for further study. Astro, astrocyte; CPS, continuous pseudo-progression score; CT, corticothalamic; endo, endothelial; ET, extratelencephalic; IT, intratelencephalic; micro, microglia; oligo, oligodendrocyte; NP, near- projecting; OPC, oligodendrocyte precursor cell; PVM, perivascular macrophage; snRNA-seq, single-nucleus RNA sequencing; VLMC, vascular leptomeningealcell.

Fig. 2|. SEA-AD data portal and resources.

a-f, Resources and tools available through the SEA-AD portal enable users to: view donor metadata and neuropathology images (a); perform comparative analysis of molecular differences in disease state (b); investigate molecular changes within cell types with respect to neuropathology and pseudotime progression (c); integrate with the Allen Brain Cell Atlas for whole-brain single-cell expression and spatial transcriptomics (d); use the MapMyCells tool for mapping user data to the BICAN standard atlas in the MTG (e); have access to data, summaries and documentation with links to external resources through Sage Bionetworks AD Knowledge Portal, Open Data on AWS and SEA-AD.org (f).