Researchers from the Allen Institute for Brain Science, Kaiser Permanente Washington Health Research Institute (KPWHRI), and UW Medicine have created the most detailed picture yet of how Alzheimer’s disease progresses at the cellular level.
“This work advances our understanding of how the brain changes when Alzheimer’s disease starts and as it advances,” said KPWHRI Principal Collaborative Scientist Nicole Gatto, PhD, MPH, an author on the study. Other KPWHRI coauthors were Project Managers Lynn Fleckenstein and Kelly Meyers.
Using data and samples from volunteers, including Kaiser Permanente Washington members participating in the Adult Changes in Thought Study (ACT Study), the researchers used advanced genomic technologies and machine learning models to create a timeline of the cellular and molecular changes caused by the disease. In the process, they found that a type of inhibitory neuron (the somatostatin-expressing inhibitory neuron) is one of the earliest cell types that is lost in Alzheimer’s disease — a surprising discovery that could highlight potential targets for future therapies.
The study, published in Nature Neuroscience, analyzed over 3.4 million cells from 84 donated brains, most from volunteers in the ACT Study. Many ACT Study participants, who may or may not develop dementia, agree to donate their brain to research after their death. By making this massive dataset available through the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) consortium, supported through the National Institute on Aging, the scientists hope to accelerate global research.
