<table class="infobox infobox-institution">
<tr>
<th class="infobox-header" colspan="2">Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD)</th>
</tr>
<tr> [@gabitto2024]
<td class="infobox-image" colspan="2"> [@allen2024]
<em>No official project logo is published on SEA-AD consortium source pages.</em> [@nih2024]
</td> [@registry]
</tr> [@niagads]
<tr> [@allen2024a]
<td class="label">Type</td> [@allen2026]
<td>Multi-institutional Research Consortium</td> [@seaad2026]
</tr>
<tr>
<td class="label">Lead Institution</td>
<td>[Allen Institute for Brain Science](/institutions/allen-institute)</td>
</tr>
<tr>
<td class="label">Partners</td>
<td>University of Washington ADRC<br>Kaiser Permanente Washington HRI</td>
</tr>
<tr>
<td class="label">Funding</td>
<td>NIH/NIA U19AG060909 ($40.7M)</td>
</tr>
<tr>
<td class="label">Disease Focus</td>
<td>[Alzheimer's Disease](/diseases/alzheimers)</td>
</tr>
<tr>
<td class="label">Data Modalities</td>
<td>snRNA-seq, snATAC-seq, MERFISH, WGS, Neuropathology</td>
</tr>
<tr>
<td class="label">Cells Profiled</td>
<td>>3.4 million</td>
</tr>
<tr>
<td class="label">Donors</td>
<td>84 (spanning AD spectrum)</td>
</tr>
<tr>
<td class="label">Data Portal</td>
<td><a href="https://portal.brain-map.org/explore/seattle-alzheimers-disease" target="_blank">portal.brain-map.org/SEA-AD</a></td>
</tr>
<tr>
<td class="label">Key Publications</td>
<td>Gabitto et al., <em>Nature Neuroscience</em> 2024</td>
</tr>
</table>
<table class="infobox infobox-institution">
<tr>
<th class="infobox-header" colspan="2">Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD)</th>
</tr>
<tr> [@gabitto2024]
<td class="infobox-image" colspan="2"> [@allen2024]
<em>No official project logo is published on SEA-AD consortium source pages.</em> [@nih2024]
</td> [@registry]
</tr> [@niagads]
<tr> [@allen2024a]
<td class="label">Type</td> [@allen2026]
<td>Multi-institutional Research Consortium</td> [@seaad2026]
</tr>
<tr>
<td class="label">Lead Institution</td>
<td>[Allen Institute for Brain Science](/institutions/allen-institute)</td>
</tr>
<tr>
<td class="label">Partners</td>
<td>University of Washington ADRC<br>Kaiser Permanente Washington HRI</td>
</tr>
<tr>
<td class="label">Funding</td>
<td>NIH/NIA U19AG060909 ($40.7M)</td>
</tr>
<tr>
<td class="label">Disease Focus</td>
<td>[Alzheimer's Disease](/diseases/alzheimers)</td>
</tr>
<tr>
<td class="label">Data Modalities</td>
<td>snRNA-seq, snATAC-seq, MERFISH, WGS, Neuropathology</td>
</tr>
<tr>
<td class="label">Cells Profiled</td>
<td>>3.4 million</td>
</tr>
<tr>
<td class="label">Donors</td>
<td>84 (spanning AD spectrum)</td>
</tr>
<tr>
<td class="label">Data Portal</td>
<td><a href="https://portal.brain-map.org/explore/seattle-alzheimers-disease" target="_blank">portal.brain-map.org/SEA-AD</a></td>
</tr>
<tr>
<td class="label">Key Publications</td>
<td>Gabitto et al., <em>Nature Neuroscience</em> 2024</td>
</tr>
</table>
The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) is a large-scale, multi-institutional research consortium dedicated to gaining a deep molecular and cellular understanding of the early pathogenesis of [Alzheimer's Disease](/diseases/alzheimers-disease) (AD). The project creates the most comprehensive open-access cellular atlas of AD, integrating neuropathology, single-cell and spatial genomics, whole genome sequencing, and longitudinal clinical metadata from human brain tissue spanning the full spectrum of Alzheimer's Disease pathology [@hawrylycz2024].
SEA-AD is led by the [Allen Institute for Brain Science](/institutions/allen-institute) in collaboration with the University of Washington Alzheimer's Disease Research Center (UW ADRC) and the Kaiser Permanente Washington Health Research Institute, which operates the Adult Changes in Thought (ACT) longitudinal aging study. The project is supported by the National Institute on Aging (NIA) under award U19AG060909. As of 2026, public consortium resources remain active (including a refreshed SEA-AD portal and a 2026 consortium/SAB update meeting), so prior wording that implied work ended in 2025 should be interpreted as the initial award-cycle framing rather than project closure["@seattle"][@allen2026][@seaad2026] [@seattle].
The consortium's goal is to identify which brain cell types are affected earliest in AD, what molecular changes drive the disease, and how these changes relate to the progression of [amyloid plaques](/mechanisms/amyloid-hypothesis), [tau tangles](/mechanisms/tau-pathology), and [cognitive decline](/srp19---signal-recognition-particle-19). By making all data freely available, SEA-AD aims to accelerate the development of cell-type-specific therapeutic targets for AD.
The [Allen Institute for Brain Science](/institutions/allen-institute) serves as the lead institution, providing expertise in large-scale single-cell genomics, spatial transcriptomics, and data integration. Key Allen Institute investigators include:
The UW Alzheimer's Disease Research Center provides clinical expertise, neuropathological assessment, and access to brain tissue from research participants with well-characterized clinical histories. The UW ADRC contributes post-mortem brain tissue with extensive antemortem clinical data including cognitive assessments and medical history.
The Adult Changes in Thought (ACT) study, based at Kaiser Permanente Washington, is a long-running prospective cohort study that has followed thousands of older adults in the Seattle area since 1994. ACT participants contribute to SEA-AD by providing longitudinal cognitive data and consenting to brain donation upon death, enabling researchers to link cellular changes to clinical progression over years or decades [@kukull2002].
SEA-AD integrates an unprecedented breadth of data types from each donor brain, enabling multiscale analysis from molecules to cells to tissue architecture:
Using 10x Genomics Chromium technology, researchers have profiled gene expression from millions of individual nuclei isolated from the middle temporal gyrus (MTG) of 84 donors. Over 36,000 genes are evaluated per nucleus, enabling identification of more than 100 cell types in each cortical area assayed. This includes all major neuronal subtypes (excitatory and inhibitory), [astrocytes](/cell-types/astrocytes), [oligodendrocytes](/cell-types/oligodendrocytes), [microglia](/cell-types/microglia) plaque density and distribution
Each donor's brain tissue is accompanied by longitudinal clinical data including cognitive test scores, dementia diagnosis history, comorbidities, medications, and demographic information. This linkage between molecular data and clinical phenotype is critical for understanding how cellular changes drive the clinical progression of AD [@kukull2002].
The SEA-AD consortium's landmark paper, published in Nature Neuroscience in October 2024 by [Gabitto](/researchers/mariano-gabitto), [Travaglini](/researchers/kyle-travaglini), Rachleff et al., analyzed 3.4 million brain cells from 84 donors and revealed that Alzheimer's Disease progresses through two distinct phases [@gabitto2024]:
Early Phase (Slow Pathology Accumulation):
A key finding of the SEA-AD study was that somatostatin-expressing (SST+) inhibitory interneurons are selectively lost in the earliest phase of AD — before the widespread excitatory neuron death that characterizes later stages. This was unexpected, as most prior research had focused on excitatory neurons and [cholinergic neurons](/cell-types/cholinergic-neurons) as the primary casualties of AD [@gabitto2024].
The researchers hypothesize that loss of SST+ inhibitory neurons may trigger a cascade of dysfunction: disrupting the balance between excitation and inhibition in cortical circuits, leading to hyperexcitability, aberrant neural activity, and ultimately widespread network collapse. This finding has implications for understanding epileptiform activity observed in early AD and may point to new therapeutic targets [@allen2024].
By combining snRNA-seq and snATAC-seq (Multiome) data, SEA-AD has identified disease-associated changes in gene regulatory programs that are specific to individual cell types. For example, [microglia](/entities/microglia) show activation of inflammatory pathways (including complement, cytokine signaling, and phagocytosis genes), while [astrocytes](/entities/astrocytes) show changes in glutamate metabolism and calcium signaling genes [@gabitto2024].
MERFISH spatial transcriptomics data reveals how cell types are reorganized around pathological features. Disease-associated [microglia](/cell-types/microglia)/cell-types/microglia cluster near amyloid plaques, while reactive [astrocytes](/cell-types/astrocytes) form a surrounding layer — creating a "cellular halo" of inflammation around each plaque. These spatial patterns intensify with disease severity [@gabitto2024].
The SEA-AD findings have significant implications for therapeutic development:
All SEA-AD data is freely available to the research community through multiple portals:
SEA-AD is part of a broader ecosystem of brain cell atlas projects:
The study of Seattle Alzheimer'S Disease Brain Cell Atlas (Sea Ad) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
The following diagram shows the key molecular relationships involving Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) discovered through SciDEX knowledge graph analysis: