New! SEA-AD Multiregion and Caudate data now explorable in ABC Atlas

The ABC Atlas has been updated with new data!

Two new data sets from the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) are now explorable: SEA-AD Multiregion and SEA-AD CaH.

SEA-AD Multiregion Taxonomy
Alzheimer’s disease (AD) is characterized by the progressive accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau (pTau) tangles across brain regions. While these regions differ in architecture, function, and susceptibility to pathology, many share common cellular populations. The SEA-AD Multiregion Taxonomy was developed to provide a unified cellular framework for studying cellular vulnerability and molecular change across the full arc of canonical AD progression.

This taxonomy is derived from a multimodal dataset generated from 84 deeply characterized donors spanning the full spectrum of AD pathology. The dataset presented here contains approximately 6 million high-quality nuclei from single-nucleus RNA-seq and Multiome profiling, along with an additional 2.6 million nuclei that did not pass quality-control criteria. These data were generated alongside approximately 1 million single-nucleus ATAC-seq profiles, which informed multimodal analyses but are not included in the resources described here. Single-nucleus profiling was performed across ten brain regions: medial entorhinal cortex (MEC), lateral entorhinal cortex (LEC), hippocampus (HIP), inferior temporal gyrus (ITG), middle temporal gyrus (MTG), superior temporal gyrus (STG), dorsolateral prefrontal cortex (BA9), frontal insula (FI), angular gyrus (AnG), and primary visual cortex (V1C). Nuclei were mapped to an expanded reference taxonomy comprising 207 cell types, organized into 28 subclasses and 3 major cellular classes, including both broadly shared and regionally specialized populations. Cell type names are harmonized between studies; for example, Sst 25 from Gabitto, Travaglini et al. (2024) and Sst 25 in this taxonomy refer to the same cell population.

SEA-AD Caudate Nucleus snRNA-seq Atlas
The caudate nucleus (Ca) is a “C”-shaped subcortical structure that pairs with the putamen to form the striatum, a component of the basal ganglia. Beyond its role in motor control, the caudate participates in cognitive processes such as procedural memory and associative learning, and it is implicated in several neurodegenerative diseases, including Parkinson’s, Huntington’s, and Alzheimer’s. In Alzheimer’s specifically, the presence of amyloid-β plaques in the head of the caudate partly defines Thal stage III. Here we introduce the SEA-AD Caudate Head Atlas, a cellular-resolution view of Alzheimer’s disease pathology in the caudate head of human donors.

This dataset comprises ~800,000 single nuclei from a 42-donor subset of the original 84-donor SEA-AD cohort, selected to minimize comorbidities with other known brain diseases. Disease progression is quantified with a continuous pseudo-progression score (CPS), derived from a biophysical model of disease progression fit to quantitative neuropathology from the region. Standard staging measures are also included: overall AD neuropathologic change (ADNC), Braak, and Thal. To annotate the data, we integrated two references, the Human and Mammalian Brain Atlas (HMBA) of the basal ganglia and the SEA-AD middle temporal gyrus (MTG) atlas, merging overlapping classes into the SEA-AD taxonomy. Quality control was performed after integration: for each cluster, thresholds were set on standard metrics including Genes Detected, Doublet score, and Fraction mitochondrial UMIs. Please note that while we release all cells through abc_atlas_access, the cells visualized here are only those are used in the analysis presented in the paper.

Both data sets carry donor-level clinical and neuropathological metadata alongside the taxonomy, so you can color and filter cells by CPS, Braak, Thal, CERAD score, APOE Genotype, Cognitive Status, LATE, and more. Definitions of many of these features can be found here.

Explore this data now in the ABC Atlas!

Other resources related to this release:

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