Description

The Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) consortium strives to gain a deep molecular and cellular understanding of the early pathogenesis of Alzheimer’s disease by building a detailed map of brain cell types and how they are impacted by disease. The SEA-AD project integrates several data modalities including next-generation single-cell/nucleus molecular profiling, spatial transcriptomics, quantitative neuropathology, whole genome sequencing (WGS), and deep clinical phenotyping. The SEA-AD consortium is based at the Allen Institute for Brain Science in collaboration with the University of Washington Alzheimer’s Disease Research Center and the Adult Changes in Thought (ACT) study from Kaiser Permanente Washington Health Research Institute. The consortium provides free, open resources and data to the scientific community, and is supported by the National Institute on Aging (NIA). 

Postmortem brain tissue and donor metadata were obtained via the UW BioRepository and Integrated Neuropathology (BRaIN) laboratory from participants in the Kaiser Permanente Washington Health Research Institute ACT Study and the University of Washington ADRC. The study cohort was selected based solely on donor brains undergoing precision rapid procedure (optimized tissue collection, slicing and freezing) during an inclusion time period at the start of the SEA-AD study, excluding those with a diagnosis of frontotemporal lobar degeneration, Down syndrome, amyotrophic lateral sclerosis or other confounding degenerative disorder (not including Lewy body disease, limbic-predominant TDP-43 encephalopathy or microvascular brain injury). The cohort was chosen in this manner to represent the full spectrum of AD neuropathology, with or without common comorbid age-related pathologies. No randomization was used in cohort selection. The experimental donor cohort contains 84 donors, 51 females and 33 males, aged 65–102 (mean 88). The 84 donors span the spectrum of AD pathology, from those without AD/dementia to those with dementia and high AD pathology. More information available at SEA-AD.org. 

Principal Investigators

  • Ed Lein — Allen Institute for Brain Science
  • C. Dirk Keene — University of Washington
  • Michael Hawrylycz — Allen Institute for Brain Science
  • Rebecca Hodge — Allen Institute for Brain Science
  • Jeremy Miller — Allen Institute for Brain Science
  • Jennie Close — Allen Institute for Brain Science
  • Gerard D. Schellenberg — University of Pennsylvania

Funding Sources

The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) consortium is supported by the National Institute on Aging (NIA) grant U19AG060909. The study data were generated from postmortem brain tissue donated to the University of Washington BRaIN laboratory and Precision Neuropathology Core, which is supported by the UW ADRC (NIA grant no. P30AG066509, previously no. P50AG005136), the ACT study (NIA grant no. U19AG066567) and U24AG072458, U24NS135561, U24NS133945, U24NS133949, RF1AG065406, R01NS105984, R01AG60942 and UM1MH130981. Additionally, ACT data collection for this work was supported, in part, by prior funding from the NIA (no. U01AG006781) and the Nancy and Buster Alvord Endowment (to C. Dirk Keene). The Alzheimer’s Disease Genetics Consortium (ADGC grant U01AG032984) funded whole genome sequencing and genotyping of the samples. The Genome Center for Alzheimer’s Disease (GCAD grant U54AG052427) processed the data.

Publications

  • Hawrylycz M. SEA-AD is a multimodal cellular atlas and resource for Alzheimer's disease. Nature aging. 2024 Oct. PubMed link
  • Gabitto MI. Integrated multimodal cell atlas of Alzheimer's disease. Nature neuroscience. 2024 Dec. PubMed link