Neuroscientists at the Allen Institute for Brain Science and their collaborators have released their first research data set on Alzheimer’s disease, in which they categorized cell types based on gene activity. The team hope this approach could ultimately identify new targets for better therapies.
The publicly available dataset captures large-scale cellular and molecular information gleaned from more than 1.2 million neurons and other brain cells from 84 people who donated their brains to science after their deaths. It includes detailed microscopy images of amyloid-β and other disease-related proteins in the patients’ brains.
“We’ve made really remarkable progress in developing new tools to study the human brain, and this really opens up whole new possibilities for studying disease,” said Ed Lein, PhD, lead investigator of the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) team, which released the new data.
“As we’ve developed these tools, it became apparent that we could have a big impact by creating a much higher resolution atlas of what Alzheimer’s actually looks like at the cellular level,” added Lein, who is also senior investigator at the Allen Institute for Brain Science.
The SEA-AD, is a National Institute on Aging-funded collaboration headquartered at the Allen Institute, with additional research projects at University of Washington (UW) Medicine and Kaiser Permanente Washington Health Research Institute.
The cellular techniques used in the consortium build off previous work at the Allen Institute and elsewhere, through the NIH-funded BRAIN Initiative.
“Because we don’t know yet which of many possible pathways are most important in Alzheimer’s, we need to have the most comprehensive picture we possibly can of the related changes in brain cells,” said Richard J. Hodes, MD, Director of NIH’s National Institute on Aging. “Progress such as this means we have an increased understanding of what underlies the disease, and therefore a better hope for strategizing to effectively prevent and treat it.”
Alzheimer’s disease affects more than 6 million Americans and is the most common cause of dementia. Scientists have long thought amyloid plaques were the root cause of Alzheimer’s. But several recently developed drugs that break up amyloid plaques have had minimal, if any, effect on disease progression. Studies have pointed to genetic roots for the disease and have uncovered as many as 42 genes linked to Alzheimer’s pathology.
The SEA-AD team wanted to start from the beginning, and identify the individual brain cells that die or change as Alzheimer’s progresses.
In this first data release, which analyzes cells from the middle temporal gyrus, the team identified certain kinds of neurons that are selectively vulnerable to the disease, while other kinds of brain cells increase in abundance.
“This data release is the first of many. My hope is that with this release and future releases, we will generate data that will give us clues as to how this disease actually works,” said C. Dirk Keene, MD, PhD, Professor and Nancy and Buster Alvord Endowed Chair of Neuropathology at UW Medicine and one of the investigators involved in the data release.
The team identified certain kinds of neurons that are selectively vulnerable to the disease, while other kinds of brain cells increase in abundance. The data release opens SEA-AD data and resources to the general scientific community for anyone to explore and includes:
- A transcriptomics comparative viewer.
- A transcriptomic explorer.
- A donor index and neuropathology image viewer.
- A link to the SEA-AD transcriptomics data in the Chan Zuckerberg CELL by GENE
- A link to the SEA-AD chromatin accessibility data in the UC Santa Cruz’s Genome Browser.